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From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com>
Newsgroups: sci.med.nutrition
Subject: Re: Safety of Statins
Date: Thu, 15 Aug 2002 17:47:09 -0700
Message-ID: <ajhi3e$qgh$1@slb6.atl.mindspring.net>
Al Hephy wrote in message <1029423201.460138@savina>...
>"SAFE" is a relative term sometimes used to mean 'doesn't kill many'
>people. Some authorities are dead set against 'statins.
Yep. The dumb ones.
>They work by interfering with liver function and some people who are
otherwise in good health can handle them for a while.
They work by interfering with a certain enzyme. That's a long way from
saying they interfere with liver "function."
> Others get adverse reactions quickly.
Rarely.
>Long term effects have never been adequately established. <
We know more about the long term effects of statins than most other drugs.
>There are less risky alternatives. Investigate them.
You can't prove there are less risky alternatives, because nobody has ever
done a long term study directly comparing statin use to any other method of
lowering cholesterol, or treating heart disease.
We do know that statins are less risky than doing nothing. And we know that
risk reduction for statin use is of the order of 25% in death risk. I don't
think you can find me numbers that good for any diet, including the Ornish
diet.
SBH
--
I welcome email from any being clever enough to fix my address. It's open
book. A prize to the first spambot that passes my Turing test.
From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com>
Newsgroups: sci.med
Subject: Re: Word for the day ("Ignorance")
Message-ID: <occD9.2763$It3.247412@newsread2.prod.itd.earthlink.net>
Date: Thu, 21 Nov 2002 21:26:44 GMT
KyroDoc wrote in message <20021121144835.00474.00000039@mb-fl.aol.com>...
>Oh and cholesterol lowering drugs have been linked to liver cancer too...
In rodents. So if you're a rat and are taking cholesterol lowering drugs, be
wary. Rodents are very susceptible to liver cancer. In fact, if you do life
span studies on rodents, a regular 10 to 20% will die of liver cancer even
if you feed them nothing but regular diet and no additives at all. Do you
see that happening in people? No, you don't.
Analysis and meta analysis of all the largest and longest statin trials has
found NO evidence of increase in any kind of cancer, and specifically not in
liver cancer. So that's it. They continue to look, but so far all they've
found in statin trials is people being saved from heart disease and stroke,
and living longer than the placebo group.
>But ya know...It's allll in the name of good science because hey after all
>high cholesterol causes heart attacks....right?
>
>Right??
Right. It's one of the causes.
>No?
>
>No you say?
I don't say no.
>Now scientists say it's inflammation of the arteries that's whats causing
>so many heart attacks????? Not the elevated LDL's?
They said no such thing. Both effects are causal, and synergisitic
(inflammatory proteins cause macrophages to take up LDL, in fact). The
statin drugs lower systemic inflammation, too, as measured by CRP and other
marker proteins for it.
Let's see your evidence that chiropractic does that.
>Which means all those people lost their lives and more have liver cancer
>from a drug that was supposed ......to but didnt...and it.......
There is no evidence that ANYBODY has lost their life to liver cancer from
taking a statin drug. Zero. Zip. Nada.
>But...the SCIENCE The SCIENCE
Is something about which you know .
>Shit.
CORRECT!
>Fortunately those poor people didnt make it onto the IOM's list of 100,000.
*ed
The IOM problems with this figure have been explained to you. It's only
100,000 if you assume that the death rate is ZERO in very ill hospitalized
people in whom a medical mistake was NOT made, vs 13% in those in whom it
was. However reasonable estimates are that death rate is about 13% in
mistake free hospitalizations also.
SBH
--
I welcome email from any being clever enough to fix my address. It's open
book. A prize to the first spambot that passes my Turing test.
From: sbharris@ix.netcom.com (Steve Harris sbharris@ROMAN9.netcom.com)
Newsgroups: sci.psychology.theory,sci.med,sci.med.cardiology
Subject: Re: Lipitor, Thief of Memory - New Book
Date: 3 Feb 2004 18:48:27 -0800
Message-ID: <79cf0a8.0402031848.79e9fdd7@posting.google.com>
"Sharon Hope" <shope@anet.net> wrote in message
news:<tBFTb.213993$na.351460@attbi_s04>...
> The new book, "Lipitor, Thief of Memory", is now available. The release is
> timely, as Wall Street Journal reported last week that the cognitive damage
> from statin drugs is seen in ~ 15% of the patients. Many of these people
> are told
> they have "early Alzheimer's" when in fact the drug is affecting their
> memory.
Comment:
Well, since you have to have more things than memory problems to
diagnose "early Alzheimer's" all this means is that the doctors
involved were fools.
If Lipitor causes memory problems in some patients, it would still not
be wise to tar all the statins with same brush. Nobody believes that
it's the fall in cholesterol per se that causes the problem, and
indeed you quote reports of people having brain problems with Lipitor
who had them resolve in Pravachol. Which is not too surprising in
light of the fact that Lipitor gets into the brain very well among
this category of drugs, while Pravachol probably is at the other end
of scale in ability to penetrate the blood brain barrier.
SBH
From: sbharris@ix.netcom.com (Steve Harris sbharris@ROMAN9.netcom.com)
Newsgroups: sci.psychology.theory,sci.med,sci.med.cardiology
Subject: Re: Lipitor, Thief of Memory - New Book
Date: 5 Feb 2004 14:05:47 -0800
Message-ID: <79cf0a8.0402051405.4f1107f8@posting.google.com>
brucebo@my-deja.com (Bruce Bowen) wrote in message
news:<b824a8a0.0402041303.2258ad11@posting.google.com>...
> sbharris@ix.netcom.com (Steve Harris sbharris@ROMAN9.netcom.com) wrote
> in message news:<79cf0a8.0402031848.79e9fdd7@posting.google.com>...
> >
> > If Lipitor causes memory problems in some patients, it would still not
> > be wise to tar all the statins with same brush. Nobody believes that
> > it's the fall in cholesterol per se that causes the problem, and
> > indeed you quote reports of people having brain problems with Lipitor
> > who had them resolve in Pravachol. Which is not too surprising in
> > light of the fact that Lipitor gets into the brain very well among
> > this category of drugs, while Pravachol probably is at the other end
> > of scale in ability to penetrate the blood brain barrier.
>
> Is it true that Lipitor crosses the blood-brain barrier? Previously,
> in response to the book I did a Google search on Lipitor +
> "blood-brain barrier" and most if not all of the info I could find
> claimed that it didn't, for example:
>
> http://hdlighthouse.org/see/drugs/lipitor.htm (an artcle on Lipitor
> and Alzheimers).
>
> ``This is an investigator-initiated study. I chose Lipitor because it
> doesn't cross the blood-brain barrier,'' Sparks said, noting that
> Pfizer decided to partly fund the study after being contacted.
COMMENT:
Yeah, I did the same and you're right. My recollection was wrong about
Lipitor penetrating the BBB. I did a search on statins and cognative
dysfunction and find that it while it has been reported (wow 60
cases), the case reports distribute nothing like the market share of
statins. Most of the reports involve Lipitor/atorvastatin and
Zocor/simvastatin, and one out of 60 was Pravachol; yet the market
share of Pravachol/pravastatin is much higher than that.
Statins have been looked at in a number of studies of cognative
function, since there is epidemiological suggestion (not proof) that
they might *prevent* Alzheimer's. Incidentally, this evidence is much
better than a bunch of case reports, so the statistical evidence that
statins lessen risk of cognative impairment is far more impressive
than the opposite. The 15% figure given earlier in this thread is
hogwash.
More careful prospective studies have failed to find any effect either
way. While that means we don't know yet whether or not statins will
prevent or slow Alzheimer's, it's excellent evidence that they can't
be causing cognative dysfunction in 15% of people treated, because if
they did, this should show up like a red light with bells and whistles
in any prospective controlled study where careful cognative assessment
is being done. A number of studies have been launched with reports
from two of them, and the claimed large (15%) effect just isn't there.
This doesn't rule out some drug specific effect (paricularly for Zocor
and Lipitor) in some (very) small numbers of users. But no such effect
has been proven in a placebo controlled study. How small the effect
might be cannot even be determined from the data we have, except that
it's too low to show up as a statistically significant effect in at
least 3 controlled studies, which means it's very low. When the below
article says the literature is conflicting regarding statins and
memory loss, it means one study showed a *trend* toward memory
impairment, but the study was so small it wasn't statistically
significant. Two larger placebo controlled studies failed to find the
effect. We don't yet understand what the discrepancy is, but a
nonsignificant trend in one small study plus 60 uncontrolled case
reports, does not an epidemic make.
Pharmacotherapy. 2003 Jul;23(7):871-80. Related Articles, Links
Statin-associated memory loss: analysis of 60 case reports and review
of the literature.
Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM.
Drug Information Service, Duke University Medical Center, Durham,
North Carolina 27710, USA.
OBJECTIVE: To review case reports of statin-associated memory loss as
well as the available published evidence for and against such a link.
METHODS: We searched the MedWatch drug surveillance system of the Food
and Drug Administration (FDA) from November 1997-February 2002 for
reports of statin-associated memory loss. We also reviewed the
published literature (using MEDLINE) and prescribing information for
these drugs. RESULTS: Of the 60 patients identified who had memory
loss associated with statins, 36 received simvastatin, 23
atorvastatin, and 1 pravastatin. About 50% of the patients noted
cognitive adverse effects within 2 months of therapy. Fourteen (56%)
of 25 patients noted improvement when the statin was discontinued.
Memory loss recurred in four patients who were rechallenged with the
drug. None of the 60 reported cognitive test results. Two
placebo-controlled trials found no benefits for statins on cognition
or disability. One randomized controlled trial of simvastatin found no
effects on cerebrospinal amyloid levels. In one small, randomized
study, patients receiving statins showed a trend toward lower
cognitive performance than those receiving placebo. Five observational
studies found a lower risk of dementia among patients receiving
statins. CONCLUSION: Current literature is conflicting with regard to
the effects of statins on memory loss. Experimental studies support
links between cholesterol intake and amyloid synthesis; observational
studies indicate that patients receiving statins have a reduced risk
of dementia. However, available prospective studies show no cognitive
or antiamyloid benefits for any statin. In addition, case reports
raise the possibility that statins, in rare cases, may be associated
with cognitive impairment, though causality is not certain.
Publication Types:
Review
Review, Multicase
Review, Tutorial
PMID: 12885101 [PubMed - indexed for MEDLINE]
>
> In anycase, the anecdotes the author relates in the promo are sudden
> acute lapses in memory and/or amnesia. Not any sort of gradual
> degredation in memory, as one might expect with the hypothetical
> complaint.
>
> -Bruce
From: sbharris@ix.netcom.com (Steve Harris sbharris@ROMAN9.netcom.com)
Newsgroups: sci.psychology.theory,sci.med,sci.med.cardiology
Subject: Re: Lipitor, Thief of Memory - New Book
Date: 6 Feb 2004 15:30:51 -0800
Message-ID: <79cf0a8.0402061530.7e8ecb21@posting.google.com>
"Sharon Hope" <shope@anet.net> wrote in message
news:<hBEUb.189538$nt4.800549@attbi_s51>...
> Check your facts.
>
> The 15% figure is a Wall Street Journal quote from the principal
> investigator of a placebo-controlled 5 year NIH study, not yet published.
COMMENT:
Ahem. Check YOUR facts. First of all, if it's something an
investigator told a news journalist about unpublished data one time,
it's not a fact, it's hearsay.
Second, if you're referring to the UCSD Statin trial (the only long
NIH trial I know about) and if the investigator being quoted is Ms.
Golumb, she can't possibly know any figures, because the codes for
placebo vs. active drug in this trial won't be broken until the end of
the trial, and the trial hasn't quite ended yet. So either she didn't
say what you say she said, or else they aren't running the trial as
they promised, or else you're just wrong in many of a dozen possible
ways.
Please quote the exact WSJ text.
> The references to statins and Alzheimer's prevention are all speculative
> prefaces to funding a trial (most have a "?" in the title, as in Can
> statins...?). The one placebo-controlled trial going on right now is having
> great difficulties, because - per a published report by some of the
> physicians conducting the trial - they cannot keep the elderly participants
> on the statin drug portion of the population - they keep developing serious
> adverse effects and have to be washed out of the study.
Reference for this published report? If the trial is
placebo-controlled and double-blind, as the UCSD trial is, how do the
investigators know if the people "washing out" due to side effects are
taking active drug, or placebo?
>
> One of the studies eliminated "unrelated mortality" and included
> hemorrhagic stroke in the "unrelated" category, despite the Lipitor
> Physician's Reference stating:
> CNS Toxicity
>
>
> Brain hemorrhage was seen in a female dog treated for 3 months at 120
> mg/kg/day. Brain hemorrhage and optic nerve vacuolation were seen in another
> female dog that was sacrificed in moribund condition after 11 weeks of
> escalating doses up to 280 mg/kg/day. The 120 mg/kg dose resulted in a
> systemic exposure approximately 16 times the human plasma
> area-under-the-curve (AUC, 0-24 hours) based on the maximum human dose of 80
> mg/day. A single tonic convulsion was seen in each of 2 male dogs (one
> treated at 10 mg/kg/day and one at 120 mg/kg/day) in a 2-year study. No CNS
> lesions have been observed in mice after chronic treatment for up to 2 years
> at doses up to 400 mg/kg/day or in rats at doses up to 100 mg/kg/day. These
> doses were 6 to 11 times (mouse) and 8 to 16 times (rat) the human AUC
> (0-24) based on the maximum recommended human dose of 80 mg/day.
>
> CNS vascular lesions, characterized by perivascular hemorrhages, edema, and
> mononuclear cell infiltration of perivascular spaces, have been observed in
> dogs treated with other members of this class. A chemically similar drug in
> this class produced optic nerve degeneration (Wallerian degeneration of
> retinogeniculate fibers) in clinically normal dogs in a dose-dependent
> fashion at a dose that produced plasma drug levels about 30 times higher
> than the mean drug level in humans taking the highest recommended dose.
COMMENT:
Things that happen in dogs at blood levels 30 times higher than are
seen in humans on the drug, for long periods of time, are hardly
relevent to anything. For example, there is no animal alive which
could tolerate blood levels of aspirin 30 times those which are
therapeutic in humans, even for a few hours. But the machanisms of
salicylate toxicity in animals killed with overdoses of aspirin
(seizure, heart failure) are not relevent to human trials of
therapeutic doses of aspirin. They are simply data that are useless
for that purpose, even used inferentially. They might be helpful in
trying to evaluate suicide attempts in people taking bottles of
aspirin, but that's about it. Since I know of nobody who has tried to
kill themselves by taking a whole bottle of statin pills everyday for
three months, such a thing being done to an animal is nearly junk
science. It's an advertisement for PETA if it is used to interpret any
human data at all.
SBH
From: sbharris@ix.netcom.com (Steve Harris sbharris@ROMAN9.netcom.com)
Newsgroups: sci.psychology.theory,sci.med,sci.med.cardiology
Subject: Re: Lipitor, Thief of Memory - New Book
Date: 6 Feb 2004 18:42:59 -0800
Message-ID: <79cf0a8.0402061842.5b6e93eb@posting.google.com>
"Sharon Hope" <shope@anet.net> wrote in message
news:<_MEUb.185823$5V2.905524@attbi_s53>...
> Study is to be published, a 5 year NIH funded placebo controlled study of
> statins and non-cardiac endpoints. The quote in the Wall Street Journal was
> from the principal investigator.
>
> If you read the full study - not the abstract - of the published Muldoon
> study you will be shocked at the statin scores in comparison with the
> placebo group - and that was just a 6 month study.
> http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TDC-406793X-2
COMMENT:
Actually, there's not much that is shocking in this study. Treated
subjects failed to improve as much as expected, due to practice
effect. They didn't become blithering mentally crippled idiots, and
actually, nobody really did worse. Differences between treated and
placebo groups amount to 0.2 standard deviation in performance, which
is about like an IQ change of 2 points even if it extended to all
categories of performance, which it didn't. Statistically significant
but not clinically so. It had NO effect on quality of life, and caused
NO psychological distress. And why should it, since we're talking
about mental performance changes far smaller than are regularly
produced by a cup of coffee, or a meal?
Here's your text. And let me note that even the results below have NOT
been reproduced in other studies looking for them, so they aren't
written in stone.
SUBJECTS AND METHODS: In this double-blind investigation, 209
generally healthy adults with a serum low-density-lipoprotein (LDL)
cholesterol level of 160 mg/dL or higher were randomly assigned to
6-month treatment with lovastatin (20 mg) or placebo. Assessments of
neuropsychological performance, depression, hostility, and quality of
life were conducted at baseline and at the end of the treatment
period. Summary effect sizes were estimated as z scores on a standard
deviation (SD) scale.
RESULTS: Placebo-treated subjects improved between baseline and
posttreatment periods on neuropsychological tests in all five
performance domains, consistent with the effects of practice on test
performance (all P <0.04), whereas those treated with lovastatin
improved only on tests of memory recall (P = 0.03). Comparisons of the
changes in performance between placebo- and lovastatin-treated
subjects revealed small, but statistically significant, differences
for tests of attention (z score = 0.18; 95% confidence interval (CI),
0.06 to 0.31; P = 0.005) and psychomotor speed (z score = 0.17; 95%
CI, 0.05 to 0.28; P = 0.004) that were consistent with greater
improvement in the placebo group. Psychological well-being, as
measured several ways, was not affected by lovastatin.
CONCLUSION: Treatment of hypercholesterolemia with lovastatin did not
cause psychological distress or substantially alter cognitive
function. Treatment did result in small performance decrements on
neuropsychological tests of attention and psychomotor speed, the
clinical importance of which is uncertain.
COMMENT: The above is the study author's conclusion, remember, not
mine.
SBH
From: sbharris@ix.netcom.com (Steve Harris sbharris@ROMAN9.netcom.com)
Newsgroups: sci.psychology.theory,sci.med,sci.med.cardiology
Subject: Re: Lipitor, Thief of Memory - New Book
Date: 9 Feb 2004 13:30:23 -0800
Message-ID: <79cf0a8.0402091330.2dae6dc5@posting.google.com>
"Sharon Hope" <shope@anet.net> wrote in message
news:<ioFVb.7161$032.28235@attbi_s53>...
> This was a 6 month study, and already there was a statistically significant
> difference. Statin drugs are prescribed for ongoing usage, not just for 6
> months.
COMMENT:
By what right do you use the word "already"? That presumes that which
remains to be proven, namely that the effect described is ongoing and
cumulative over longer periods of time.
Let me show you what happens if you use your style of argument. I give
one group of people a placebo and the other a blood pressure pill. At
six months I measure their blood pressures and find a significant
difference. "Oh, no!", I say. "Already at 6 months their blood
pressures are down by 5 points! At this rate, in 5 years they'll all
be dead!"
The analogy is actually fairly close, because it takes the brain a bit
to adapt to the effects of lots of drugs, including blood pressure
pills. For some months after lowering a person's blood pressure from
high to normal you can find a range of mildly negative mental effects.
But they're not usually clinically significant, and the brain does
adapt to the normal perfusion pressure, eventually. So the short term
effects by no means show that lowering blood pressure to normal is a
bad thing to do.
Very similar things happen, BTW, when you lower the blood sugars of
long uncontrolled diabetics to normal. Mentally they can have problems
for quite some time. But that doesn't mean it lasts forever, or gets
worse. And it doesn't mean you shouldn't do it. On the contrary if you
leave blood sugar (or blood pressure or blood cholesterol) high, bad
things happen to mentation in the end, because the risk of stroke is
greatly increased.
Say, did I tell you about the patient I once tried to cure of smoking?
After a 3 days without cigarettes she was complete mass of nerves,
unable to think or perform. So we had to give them back. At that
rate, in a month we'd have had to put her in a nursing home.
SBH
From: sbharris@ix.netcom.com (Steve Harris sbharris@ROMAN9.netcom.com)
Newsgroups: sci.psychology.theory,sci.med,sci.med.cardiology
Subject: Re: Lipitor, Thief of Memory - New Book
Date: 10 Feb 2004 12:17:14 -0800
Message-ID: <79cf0a8.0402101217.2aa45b0c@posting.google.com>
"Sharon Hope" <shope@anet.net> wrote in message
news:<d1YVb.214613$nt4.1033451@attbi_s51>...
> Low cholesterol and violent crime.
>
> Golomb BA, Stattin H, Mednick S.
> PMID: 11104842
> Department of Medicine, University of California, Los Angeles, CA
> 92093-0995, USA. bgolomb@ucsd.edu
>
> BACKGROUND: Community cohort studies and meta-analyses of randomized trials
> have shown a relation between low or lowered cholesterol and death by
> violence (homicide, suicide, accident); in primates, cholesterol reduction
> has been linked to increased behavioral acts of aggression (Kaplan J, Manuck
> S. The effects of fat and cholesterol on aggressive behaviour in monkeys.
> Psychosom. Med 1990;52:226-7; Kaplan J, Shively C, Fontenot D, Morgan T,
> Howell S, Manuck S et al. Demonstration of an association among dietary
> cholesterol, central serotonergic activity, and social behaviour in monkeys.
> Psychosom. Med 1994;56:479-84.). In this study we test for the first time
> whether cholesterol level is related to commission of violent crimes against
> others in a large community cohort.
> ...
> RESULTS: One hundred individuals met criteria for criminal violence. Low
> cholesterol (below the median) was strongly associated with criminal
> violence in unadjusted analysis (Men: risk ratio 1.94, P=0.002; all subjects
> risk ratio 2.32, P<0.001). Age emerged as a strong confounder. Adjusting for
> covariates using a matching procedure, violent criminals had significantly
> lower cholesterol than others identical in age, sex, alcohol indices and
> education, using a nonparametric sign test (P=0.012 all subjects; P=0.035
> men). CONCLUSIONS: Adjusting for other factors, low cholesterol is
> associated with increased subsequent criminal violence.
COMMENT:
Ms. Golumb seems to be on an anticholesterol campaign. Alas, there are
a couple of obvious confounders other than age, sex, education, and
alcohol use. After all, we need to wonder about WHY it's important to
adjust for age and sex when looking at cholesterol and violence. One
reason is that testosterone has bad effects on cholesterol,
particularly HDL. And so does age, but much of the age effect is due
to obesity. Young fat men with low testosterone aren't as violent as
young skinny men with high testosterones. But they also have higher
cholesterols, and if you don't control for body mass index and
testosterone levels, it looks like cholesterol is the culpret.
Let me put it another way: cholesterol levels are a proxy for whether
or not you're being starved, which tends to make people cranky and
violent (monkeys too). Anybody who's had to live with somebody on a
crash diet knows this effect. It's not new, either. "Yond Cassius has
a lean and hungry look; He thinks too much: such men are dangerous."
Shakespeare's Ceasar may have been on to something, but it wasn't
necessarily the effect of cholesterol.
SBH
From: sbharris@ix.netcom.com (Steve Harris sbharris@ROMAN9.netcom.com)
Newsgroups: sci.psychology.theory,sci.med,sci.med.cardiology
Subject: Re: Lipitor, Thief of Memory - New Book
Date: 10 Feb 2004 20:00:16 -0800
Message-ID: <79cf0a8.0402102000.42ccc3f@posting.google.com>
Don Kirkman <donkirk@covad.net> wrote in message
news:<g7mi201p8fhfv44g8efhlc8acnbkunm3e2@4ax.com>...
> >Wall Street Journal has run several articles by Tara Parker-Pope.
>
> Parker-Pope wrote on August 5, 2003, about CRP and cholesterol *testing*
> (she supports CRP); statins were only mentioned in passing.
>
> On January 26, 2004, Parker-Pope wrote of a number of "medical
> breakthroughs" expected in 2004. Regarding the NIH study of statins,
> she cited Beatrice Golomb, director of the study thus: "Although the
> patient data in the NIH study is still secret, Dr. Golomb says that
> among ***other*** patients she has seen, about 15% have developed some
> cognitive problem related to statin use.
Italics added by me. This is *not* the study result, which is still
sealed exactly as I said, but personal estimation of the axe-to-grind
Ms. Golumb from her private practise. Figures from her own practice,
but which she hasn't published.
From my private practice, I estimate significant mental problems with
statins are closer to zero. Take that, Dr. Golumb. Of course, I will
admit that I use Pravachol first, and that I think I've seen a lot
more rheumatic problems from the other statins than most studies will
admit. But take anecdotal evidence for what it's worth. Which is not a
lot.
> Note that the 15% is not from the NIH study but is Dr. Golomb's estimate
> from her own practice. Also note that 15% could be three patients out
> of twenty, and that Dr. Golomb's clientele may not be typical, since she
> is associated with a university.
Exactly.
> Please point us to any media actually reporting 15 or 16 million
> debilitated by statins. That's how many there would have to be for the
> 15% bad side effects you posted about. ISTM numbers like that would be
> everywhere in the media. As I wrote above, I see NO figures except Dr.
> Golomb's estimate of 15%.
Which isn't from the NIH study. Which Shirley said it was. Golly,
we're so surprised. She was wrong. It's hearsay.
SBH
From: sbharris@ix.netcom.com (Steve Harris sbharris@ROMAN9.netcom.com)
Newsgroups: sci.med
Subject: Re: selenoprotein inhibition and statins
Date: 14 Jun 2004 14:49:54 -0700
Message-ID: <79cf0a8.0406141349.2b30f13b@posting.google.com>
zwalanga@yahoo.com (Zee) wrote in message
news:<e5f4a9c2.0406132044.bc95dea@posting.google.com>...
> LANCET: conflicting ideas on statins and cancer
> Jun 11, 2004
>
> Conflicting ideas on statins and cancer
>
> www.theheart.org (behind subscription)
>
> New Orleans, LA and Lausanne, Switzerland - There have been
> conflicting reports this week on the role of statins and the
> development of cancer.
COMMENT:
Yes, conflicting ideas. One set of ideas based on actual data from
human trials, and the other based solely on somebody's blue-sky
unproven pet mechanistic hypothesis, which has no backing even from
animal studies, and in humans is not only not consistent with the
data, but actually conflicts with it. So you see that the opinions of
scientists are not exactly of the same quality.
> A case control study presented during the American Society of Clinical
> Oncology (ASCO) meeting held earlier this week in New Orleans
> suggested that statins may prevent colorectal cancer, but a letter in
> the June 12, 2004 issue of the Lancet raises the idea that statins
> could actually trigger some types of cancer as well as autoimmune
> disease.
>
> A 51% reduction in the risk of colorectal cancer
> The case control study, presented at ASCO by Dr Stephen Gruber
> (University of Michigan, Ann Arbor), involved 1849 Israeli colorectal
> cancer patients (cases) and 1959 healthy controls matched for age,
> gender, and ethnic origins. The use of statins for at least five years
> was associated with a 51% reduction in the risk of colorectal cancer,
> with statins being used by 11.3% of controls and 5.8% of cases.
>
> Gruber commented: "These observational data suggest that statins
> deserve further investigation in chemoprevention and therapeutic
> clinical trials." He added that the use of nonstatin
> cholesterol-lowering agents was not associated with reduced risk of
> colorectal cancer, suggesting that the protective effect was due to
> the statins rather than to the reduction in cholesterol. Gruber also
> noted that statins inhibit RAS and RhoA, two proteins that are
> potentially carcinogenic.
COMMENT:
I'm surprised non-statin anti-cholesterol drugs didn't actually
INCREASE GI cancers, since that is what has happened in animal
studies, and in more than one human trial. The fibrate class of drugs
in particular should be removed from the market.
> ***************************
>
> Inhibition of selenoprotein
> However, in a letter in this week's Lancet, Dr Bernard Noël (Centre
> Hospitalier Universitaire Vaudois, Lausanne, Switzerland) puts across
> a very different view.[1]
>
> He notes that a previous article in the Lancet has suggested that
> myopathy and some other side effects of statins might be attributable
> to inhibition of selenoprotein synthesis.
>
> He further points out that selenoprotein inhibition might heighten the
> risk of prostate and colon cancer and also trigger autoimmune
> diseases, more than 20 cases of which have been reported in patients
> treated with statins.
And unbelievably he gets away with this argument in the Lancet (albeit
in a letter). No doubt 20 cases of prostate cancer have been seen in
the thousands upon thousands of people taking statins. Nobody claimed
statins completely prevent prostate cancer. But in order to see what
impact they have, you need to compare with prostate incidence in a
control group NOT taking statins. I've been able to find two studies
which do this, and one finds on statistical increase in prostate
cancer risk in statin users, and the other actually finds a
statistically significant DECREASE in risk. So whatever Dr. Noël's pet
theories about whether or not statins "might" heighten these risks
based on some metabolic pathway he's identified, he should realize
that there's no evidence for it in the real world, and should
therefore have kept his mouth shut.
>"Further studies are, therefore, warranted to
> determine the long-term safety of these lipid-lowering agents," he [Noël]
> concludes.
COMMENT:
Of course. And they are being done. But to make a statement like this,
which suggests that none have been done yet, is completely
irresponsible. What a maroon!
1: Br J Cancer. 2004 Feb 9;90(3):635-7.
Statin use and cancer risk in the General Practice Research Database.
Kaye JA, Jick H.
Boston Collaborative Drug Surveillance Program, Boston University School
of Medicine, 11 Muzzey Street, Lexington, MA 02421, USA. jkaye@bu.edu
In a matched case-control study using the General Practice Research
Database, current statin use was not associated with a significantly
altered risk of any of 13 studied cancers. Untreated hyperlipidaemia was
associated with slightly increased risks of colon cancer (relative risk
1.8; 95% confidence interval 1.2-2.8), prostate cancer (1.5; 1.1-2.0),
and bladder cancer (1.9; 1.2-3.1).
PMID: 14760377 [PubMed - indexed for MEDLINE]
2: Epidemiology. 2002 May;13(3):262-7.
Statin use and the risk of breast and prostate cancer.
Coogan PF, Rosenberg L, Palmer JR, Strom BL, Zauber AG, Shapiro S.
Slone Epidemiology Unit, Boston University School of Medicine, Brookline,
MA 02446, USA. pcoogan@slone.bu.edu
BACKGROUND: Laboratory data suggest that the cholesterol-lowering
"statin" drugs may have chemopreventive potential against cancer at
various sites, including breast and prostate. However, in one trial of
pravastatin there was a significant excess of breast cancer in the
treatment group. In the present study, we assessed the relation of statin
use to the risk of breast and prostate cancer in our hospital-based
Case-Control Surveillance Study of Drugs and Serious Illnesses. METHODS:
Cases were 1,132 women with breast cancer and 1,009 men with prostate
cancer; controls were 1,331 women and 1,387 men admitted for conditions
unrelated to statin use. We used multivariate unconditional logistic
regression models to estimate odds ratios (ORs) and 95% confidence
intervals (CIs) for use of statins compared with no use. RESULTS: The OR
for breast cancer among statin users was 1.5 (95% CI = 1.0-2.3), largely
accounted for by an OR of 1.8 (95% CI = 0.9-3.6) among cases with
carcinoma in situ. Among invasive cases, the OR was 1.2 (95% CI =
0.7-2.0). The odds ratio for prostate cancer overall was 1.2 (95% CI =
0.8-1.7), and it was 1.4 (95% CI = 0.7-2.5) for Stage A. CONCLUSIONS:
The data from the present study do not support a protective effect of
statins against breast or prostate cancer. Detection bias is a possible
explanation for the higher ORs observed for carcinoma in situ or
early-stage cancer as compared with more invasive cancer.
PMID: 11964926 [PubMed - indexed for MEDLINE]
From: "Steve" <sbharris@ix.netcom.com>
Newsgroups: sci.med
Subject: Re: Red yeast rice story
Date: 8 Dec 2004 20:53:35 -0800
Message-ID: <1102568015.576312.61500@f14g2000cwb.googlegroups.com>
What makes you all think that the natural substance (mevastatin, which
is identical with the drug Mevacor) is without harmful effects?
Look, folks. Red rice yeast does not make mevastatin in order to lower
your cholesterol. It makes it as a natural antibiotic to poison other
yeasts. And possibly also larger animals that are trying to eat the
rice that the yeast wants.
Statins are cell-cycle disruptors. That's why they call them statins,
don't you know. To grow, cells need to make sterols and steroids, and
statins keep them from doing it. In that, they remind me of nothing so
much as small doses of chemotherapeutic agents. For example,
methotrexate. Methtrexate keeps cells from making DNA, but a small dose
of it has a somewhat similar effect on the immune system as statins do.
Fewer lymphocytes are made. Cellular immunity is disrupted. Autoimmune
diseases are modified. Voila. Including the autoimmune problems that
start with macrophage recruitment, then progress to foam cell
production, and on to atheroma.
SBH
sbharris atROMAN9.netcom.com
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: You can now verify positively if it is due to statin adverse
Date: Wed, 19 Jan 2005 19:33:14 -0500
Message-ID: <csmu8f$nh3$1@reader2.panix.com>
Sharon Hope wrote:
> One more piece of information. If your father was on a statin drug, there
> is now a way to verify if the cognitive/short-term memory loss damage is due
> to the statin adverse effects (List of statins is at the end of this
> message).
>
> Dr. Muldoon just published a second study that corroborates not only that
> people taking statins have a measurable loss of cognitive ability after only
> 6 months of treatment, he has determined the specific neuropsychological
> (NP) tests, within a battery of tests, that show statin damage. NP tests
> are standardized oral and written tests given by a neuropsychologist or a
> psychiatrist - the experience is almost like an interview.
This study indeed suggests that you can find some minor changes on
specific neuropsychological tests in patients taking statins. This may
or may not support the notion of more severe memory impairment occurring
in some people who take statins (overall, it probably doesn't tell you
much either way about severe memory loss).
One thing it definitely does not do is provide a diagnostic test for
differentiating statin-induced memory problems from other causes of
memory problems. This would require a completely different type of study
from the two that were performed by Dr. Muldoon.
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: You can now verify positively if it is due to statin adverse
Date: Fri, 21 Jan 2005 12:29:47 -0500
Message-ID: <csre7m$fhc$1@reader2.panix.com>
Sharon Hope wrote:
> "David Rind" <drind@caregroup.harvard.edu> wrote in message
> news:cspgi8$opg$1@reader2.panix.com...
>
>>Sharon Hope wrote:
>>
>>>On the contrary, it establishes a set of tests that are sensitive to
>>>statin damage.
>>
>>No, not in the sense that is usually meant when people say "sensitive" in
>>regard to a diagnostic test. The study did not look at a group of people
>>known to have statin-induced memory loss and see how often these
>>particular tests showed a problem while other tests did not, and did not
>>compare groups of people with different kinds of memory loss from known
>>causes to see if these particular tests differentiated them well. These
>>are some of the things you would need to know before using the tests to
>>try to make a dignosis of statin-induced memory loss.
>>
>>--
>>David Rind
>>drind@caregroup.harvard.edu
> Read the study, not just the abstract.
>
I had read the entire paper before I posted. What, exactly, do you find
in there that you think changes what I wrote above? Rather than
repeatedly stating or implying that I don't know what I'm talking about,
you might consider the possibility that I actually know something about
how one designs studies of diagnostic tests and that you yourself might
want to learn more about how such studies should be designed before
dismissing what I wrote.
By the way, I am not dismissing the results of Muldoon's studies. The
most likely explanation for them is a real effect. That does not mean,
however, that there is any evidence that one could use his
neurocognitive tests as a method for determining which patients with
memory loss have memory loss due to a statin. He makes no such claim in
his paper and I strongly doubt he would make such a claim if you asked him.
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: You can now verify positively if it is due to statin adverse
Date: Sat, 22 Jan 2005 22:41:02 -0500
Message-ID: <csv6g7$q8u$1@reader2.panix.com>
Hawki63 wrote:
>>Subject: Re: You can now verify positively if it is due to statin adverse
>>effects Re: memory loss after CABG
>>From: "Sharon Hope" shope@anet.net
>>Date: 1/21/2005 8:19 P.M. Pacific Standard Time
>>Message-id:
>
>
>>The set of standardized tests he has identified as statin-sensitive,
>>taken with the rest of the standardized tests were used by him to
>>determine the existence and extent of cognitive damage among statin
>>users.
>
>
> actually these tests...standardized or other wise..."merely" test for
> cognitive damage...
>
>
>>We are in ageement he made no such claim of weeding out which memory loss
>>patients have memory loss due to the statin.
>>
>
>
> OKKKKK....so then you...and he..are saying that whilst the person took a
> statin...AND the person "measured" some cognitive decline....there is
> NOOOO way of knowing the etiology of such...yes..statin use could be the
> issue...so could a myriad of other etiologies...having a control group
> does not obviate that it HAS to be statins...
No, this isn't fair in the other direction.
This was a randomized controlled trial. The results could have been due
to chance, or they could have screwed up the way they ran the study, or
you could decide that the tests of cognitive function used in the study
don't really correlate with what is normally meant by memory loss.
But unless you think one of those things is true, the study shows that
people who were randomly assigned to receive statins did worse on
specific neurocognitive tests (after adjusting for individual baseline
results) than people receiving placebo. This is the standard way of
showing in medicine that A caused B, and by far the most likely
explanation is that statins were responsible for the effects seen. This
is particularly the case since this was essentially a repeat of an
earlier study by the same authors.
--
David Rind
drind@caregroup.harvard.edu
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med,sci.med.diseases.cancer,
misc.health.alternative,talk.politics.medicine
Subject: Re: pharma and cancer: who profits
Date: 6 Feb 2005 19:06:29 -0800
Message-ID: <1107745589.184018.255710@g14g2000cwa.googlegroups.com>
>>These companies not only profit handsomely from cancer treatments, but
some of their drugs are linked to higher cancer incidence - frequent use
of antibiotics, several anti-depressants and cholesterol lowering
"statins" are among the most recent suspects. <<
Statins have been carefully looked at in many studies this regard, and
overall, are clean. If there's any particular cancer statins cause,
they must prevent others to more than make up for it, because cancer
mortality is either unchanged or decreased in statin users, as compared
with randomized controls. There's a great deal more evidence that other
classes of anticholesterol drugs cause cancer, and even some evidence
that drinking corn oil to lower cholesterol, also does.
Statins may cause liver cancer in rodents, but just about everything
does. If humans didn't eat anything that increased the incidence of
liver cancer in rodents, we'd be on a mighty poor diet indeed. Rodents
get liver cancer if you look cross-eyed at them. Indeed, many rodent
cancers must be spontaneous, because they appear randomly (but
frequently) even when the genetically identical inbred rodents are
identically housed and identically fed purified diets in the same room.
There just aren't any other variables you can control. I've seen this
many times in mice aging studies, and it's made a deep believer out of
me that we blame genetics and environment for a lot of things--- cancer
in particular--which are really a throw of the dice. They are due to
cosmic rays or quantum mechanical effects in DNA replication, or other
things that you just cannot control. The fancy word for this is
"stochastic processes".
In humans, identical twin studies are very interesting. They show that
the genetic effect on cancer is there, but rather small. So small, it's
hard to find.
Epidemiologic studies suggest (but of course cannot prove) that
something like half of cancer is due to environmental influences. But a
large fraction of this is smoking. With some synergistic alcohol
effects in the mouth and stomach. Alcohol also seems a paricular risk
for breast cancer. And much of the rest is gross dietary effects like
calorie consumption and fat consumption. Radon seems to cause a good
fraction of the lung cancer that smoking doesn't. If you work very
hard, you can attribute some small fraction of lympomas and thyroid
cancer to radiation. However, the idea that much cancer is caused by
pharmaceuticals and pesticides and polution in general, really does not
stand up to scrutiny. Canada would spend its money better in putting
another dollar a pack tax on cigarettes. If they smoke as much in
Quebec as they do in France, any reduction in pesticides is a raindrop
in the sea.
If most cancer isn't genetic, and most of the rest that isn't due
smoking and obesity, isn't due to *other *environmental factors, then
what IS it due to? Well, look at the mice. We all would like to blame
something. The Leftists blame corporate conspiracies for all evils. The
Conservatives blame Original Sin and lack of piety. Nobody likes to
blame the roulette wheel. That makes us feel powerless.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Statins do NOT protect against Azlheimer's
Date: 12 Feb 2005 10:20:46 -0800
Message-ID: <1108232446.038670.62370@o13g2000cwo.googlegroups.com>
>>Another misleading subject line.....
The article makes it clear that there are conflicting studies: some show
no protection against dementia, others do. Obviously, much more research
is needed.
Who wouldn't hope that there *might* be some benefit from statins against
this most debilitating disease, alzheimers? <<
COMMENT:
While we're visiting this subject, let us note that Alzheimer's is
responsible for maybe half of dementia only. A large fraction of the
other half is caused by mini-strokes and vascular disease. And of
course, there's a 20 to 30% overlap of people who have both problems.
Of these, Alzheirmer's is the process I would LEAST expect statins to
interfere with. They might, but they might not. However, statins have
already show impressive anti-stroke capability, even in people with
normal cholesterol levels. So if statins do not work in slowing or
preventing progression of Alzheimer's, this in no way means we've ruled
out their role in preventing "dementia."
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Statins do NOT protect against Azlheimer's
Date: 12 Feb 2005 14:21:20 -0800
Message-ID: <1108246879.983648.77390@l41g2000cwc.googlegroups.com>
>>Second, the large trials enrolled people at high risk for
cardiovascular disease who experience benefit from statins to nonfatal
stroke, which may lead to improvements in cognition that may help to
balance out harms to cognition from other mechanisms. Although there
are trends toward increases in fatal stroke with statins in most of the
large statin trials, those who have died cannot complete cognitive
surveys.<<
COMMENT:
Sorry, but this is a bogus argument, unless you name the studies. In
the one study you DO discuss (PROSPER), there was NO possiblity that a
difference between recognized nonfatal stroke or stroke influenced the
cognitive outcome, because recognized stroke of any kind brought the
treatment and trial to a halt for the individual patient, so no
cognitive tests were done after that. All cognitive tests reported are
prior to ANY stroke endpoint. They show no difference between treatment
and placebo groups across more than 3 years of on-treatment testing
done every 3 months, including the last set of tests before treatment
end. This is NOT consistant with any negative (or positive) cognitive
effect in this population. There was no difference between groups on
the last on-treatment cognitive test (comparing groups) or the
second-to-baseline test. Both groups decline from baseline to end, but
they decline in cognitive function at the same rate.
>>Although there are trends toward increases in fatal stroke with
statins in most of the large statin trials, those who have died cannot
complete cognitive surveys.<<
COMMENT
NO. It's no use trying to make anything of a trend unless it's a trend
in large numbers of people. The other reason this argument won't run
even if testing had been done after stroke, is that when you're talking
about fatal stroke, you're talking about tiny numbers. PROSPER (for
example) is a study of 5800 people, and there were 14 (placebo) vs 22
(Pravachol) fatal strokes. Those extra 8 fatal strokes are not
significant (p = .19) and in any case, cognitive testing NOT done on 6
dead people is certainly not going to influence any mean difference in
cognitive testing in 5800 people, even if they WERE doing testing in
non-fatal stroke patients (which they weren't), and the 8 dead stroke
patients all came from this group. Come on. Bad inferential crap like
this is why the net is called the net of a million lies. You can
sometimes get away with this stuff if nobody wants to do the work to
look the studies up, but sometimes you run afoul of people like me, who
will. So stop it.
>>The impact on total number of strokes was unaffected in the PROSPER
trial with its sole focus on the elderly population. <<
True enough. It may well be that pravachol and other statins have
significant anti-stroke effect only in other well-selected groups. None
was seen in this trial, though effect on TIAs barely missed
significance (p = 0.051 = 94.9% chance that pravachol really did
decrease TIAs in the trial).
>>In the PROSPER trial, the number of reduced transient ischemic
attacks and nonfatal strokes was actually matched by a similar number
of increased fatal strokes.<<
COMMENT:
Baloney-- that's quite wrong. The number of reduced transient ischemic
attacks was 77 (drug) vs 102 (placebo), a difference of 25, which blows
away differences in the stroke numbers (the totals for stroke plus TIA
in this study I note have been mis-done in the table, for they do not
add up to the stated drg/placebo 204/212, difference of 8, but are
actually 212/233, difference of 21). As for total strokes they were 135
(drug) vs 131 (difference of 4 in favor of placebo), which splits up
into non-fatal 116 (drug) v 119 (difference of 3 in favor of drug) and
fatal 22 (drug) vs 14 (difference of 8 in favor of placebo). These
number don't quite add up, either (there's one missing person), but
it's clear that the differences in fatal stroke numbers are too small
to decide that they simply came out of one group and went to the other.
Certainly they did NOT come out of the TIA group, for the difference of
25 there is reduced merely to 21 if you add in the total stroke
numbers. None of the stroke differences are significant, so nothing can
be said about this, either way.
>>Finally, the HPS used what is termed an "active run-in." For six weeks,
participants considered for enrollment were placed on simvastatin, and
those who were not fully compliant were dropped from the study.
Participants who perceived problems on the drug, including cognitive
problems, may have dropped the study themselves or skipped pills
intentionally. In addition, participants who developed memory problems
may have had trouble remembering to take the pills even if they did not
recognize deterioration in cognitive function. This run-in process may
have excluded participants who developed cognitive problems on the drug,
selecting only those who did not experience problems. Over one-third of
those who were interested in enrolling were excluded following this
compliance run-in.<<
COMMENT: This is an interesting hypothesis, that all the people would
had cognitive problems with statins were selected out in the first 6
weeks, and went out with the 1252 people given statin who didn't meet
inclusion criteria or who refused to participate. But anybody who
advances this argument for PROSPER had better accept the concomitant
conclusion, which is that if you *don't* have problems with statins in
6 weeks, THEN you won't have any for at least 3 years. Which is what
was then seen in the radomized 5804 people who went on to the next arm
of the trial. You can't just hypothesize parts of explanations you
like, but ignore the obligatory parts of the same hypotheses you don't.
>>Because statins reduce nonfatal stroke (and cognition is obviously not
measured in people who have experienced fatal stroke), benefits by
statins for cognitive function in those in whom a stroke was averted
might be expected.<<
COMMENT:
Nonsense, for reasons carefully explained above. The PROSPER trial
measured cognition before stroke, and also the number differences
between non-fatal and fatal stroke are non-significant. In any case,
some hypothetical raising of mean cognitive scores by killing stroke
victims is far too small to affect scoring of cognitive function in
populations of patients 360 times larger than the number of excess
stroke deaths.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Statins do NOT protect against Azlheimer's
Date: 12 Feb 2005 19:25:34 -0800
Message-ID: <1108265134.658722.162910@c13g2000cwb.googlegroups.com>
>>Steve was not refuting ME George. Steve was refuting BEA as he so
jockularly calls Dr. Beatrice Golomb, she of the 27 page cv. Hmmm.
Could Steve be envious? Nahh. Our boy got big cohones: Steve's balls
clank when he crosses a (news)room. What could it bea? <<
COMMENT:
I don't remember calling the lady "Bea." Did I really? Oh Bea-have.
My CV surely isn't 27 pages long. On the other hand, I don't have to
publish or perish, so I don't have to generated a crappy paper every
few months, in order to pad it.
I'll tell you a secret about scientific CVs. There's a big difference
between somebody who's never published in a referreed journal and
somebody who has. But not that much difference between somebody with a
dozen papers and somebody with a hundred. Fred Sanger had a one page
CV, but one paper on protein sequencing won him the Nobel prize in
1958, and another on gene sequencing won him a share of another Nobel
in 1980. Quality matters. If you're not trying to be promoted (which
Sanger wasn't), you can get some bench work done. That's a luxury fewer
and fewer people have these days.
If Dr. Golomb is a good scientist, she won't be making numerical claims
in the popular press that she hasn't published. Without seeing such a
publication, I haven't a clue as to what she means by a 20% side effect
rate. What is she counting as a side effect? A day of diarrhea? A
stuffy nose? What? Until we know, it's impossible to evaluate this
stuff, so why discuss it?
The PROSPECT study contains 8,700 patient-years of pravachol use,
compared double blind with mental status testing and ability to carry
out activities of daily living, with another 8,700 patient-years of
placebo. That's so much more experience than any given clinician ever
sees in a lifetime of prescribing any drug, that it's ridiculous. And
it's all blinded, which is a luxury no clinician gets. And they saw
nothing. And they published it. And if you don't like that, there are
20,000 patients in the HPS study, where this time they did have the
power to see stroke reduction, and did see it. But no difference in
cognitive decline, either. But no increase, either. I lay Dr.
Golomb's anecdotes along side stuff like this, and what am I supposed
to think?
If personal experience means anything, I've been prescribing statins
for a decade and half myself, and I've taken them for years. But I know
personal experience doesn't mean much. That's possibly the difference
between Dr. Golomb and myself.
SBH
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Statins do NOT protect against Azlheimer's
Date: Sat, 12 Feb 2005 23:46:59 -0500
Message-ID: <cumm44$3uh$1@reader2.panix.com>
Steve Harris wrote:
> True enough. It may well be that pravachol and other statins have
> significant anti-stroke effect only in other well-selected groups. None
> was seen in this trial, though effect on TIAs barely missed
> significance (p = 0.051 = 94.9% chance that pravachol really did
> decrease TIAs in the trial).
I agree with most of what Dr. Harris wrote in his post, but feel the
need to object to the above interpretation of p values. Assuming the
study was done correctly and pravachol really has no effect on TIAs, we
would only have expected to see a result as extreme as the result they
saw about 5.1% of the time. This is not the same as saying that there is
94.9% chance that pravachol really does decrease TIAs. You can't know
that from the study. It depends, among other things, on what the prior
probability was that pravachol decreased TIAs before the study was done.
P values deal with probabilities under the null hypothesis (no effect)
and there is no simple way to get from there to the probability you want
(that the effect seen is real).
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Statins do NOT protect against Azlheimer's
Date: Sun, 13 Feb 2005 23:42:00 -0500
Message-ID: <cupa6u$pf6$1@reader2.panix.com>
Steve Harris wrote:
> If your point is that the probability of statins influencing TIAs in
> this large randomized blinded controlled well-powered study isn't
> *exactly* the converse of the p value for rejection of the null that
> they don't, but is a bit less due to other very improbable scenarios, I
> can concede your point, and agree. I am properly chastized and
> shouldn't have used the precise 1-p number, but noted it as an
> estimate. Otherwise, I think you're being overly contrary. If you were
> *really* that epistemologically contrary in facing life, you wouldn't
> be able to function at all.
>
> SBH
No, this isn't the point I'm making, and it's a hard discussion to have
via the Web. I'll try to briefly clarify in two different ways.
1) Imagine running 20 beautifully designed randomized trials to see
whether eating bananas decreases the risk of TIAs. In the way we
currently define statistically significant, we would expect one of those
20 studies to "show" that bananas decrease the risk of TIAs purely due
to random chance. Let's say the p-value calculated in that study was
0.045. Given that you had no expectation that bananas would decrease the
risk of TIAs (not to mention 19 other negative studies), you should not
conclude that the probability that bananas decreased the risk of TIAs in
that study was 95.5%. The probability is close to 100% that bananas had
nothing to do with the decrease in TIAs in that study and that you were
seeing a statistical blip. In the other direction, imagine that instead
of bananas you were studying aspirin and got that same p-value of 0.045.
You would be wrong to conclude that based on that study the likelihood
that aspirin reduces the risk of TIAs is only 95.5%. Given all the prior
evidence that aspirin works, the probability that it worked in that
study was nearly 100%, no matter what the p-value was.
2) Think of p-values the way you think of sensitivity. That is,
sensitivity is the thing you are generally able to know about a
diagnostic test (probability that the test will be positive in someone
who has the disease), but positive predictive value is what you really
care about clinically (probability that if someone has a positive test
that they have the disease). In the same way, p-values tell you the
probability in the wrong direction -- they tell you the probability that
if nothing were going on (null hypothesis) that you would have seen the
result found in the trial. They do not tell you what the probability is
given the result found in the trial that something is going on (real
effect).
Again, remember that the way we calculate p-values, we expect a value
below 0.05 in one of twenty studies where nothing is happening. So when
someone studies 20 homeopathic remedies and one of them has finds a
p-value below 0.05, we don't want to conclude that there is better than
a 95% chance that the homeopathic preparation really worked in that
study. On the contrary, we want to recognize that the p-value does not
translate in any direct way into the probability that the homeopathic
remedy really worked.
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Statins do NOT protect against Azlheimer's
Date: Mon, 14 Feb 2005 07:48:26 -0500
Message-ID: <cuq6mu$bkp$1@reader2.panix.com>
Steve Harris wrote:
>>>Exactly right. You are perhaps the first MD I have ever seen give
> a correct interpretation of p-values. You might even know what a
> confidence interval really is! <<<
>
> COMMENT:
>
> Ahem, everything he said about p values applies equally well to
> confidence intervals, which are essentially defined by 2 p values.
> There's no way to get away from the problem here except to face it.
Yes, this is the point Jim Chinnis was presumably making. That said,
understanding the distinction between the correct interpretation of a
95% CI and the interpretation that people usually make is even trickier
than for p-values.
I'd rather stick with trying to make the argument for p-values for now,
and, if I can convince you on that, then extend the distinction to
confidence intervals. I've watched people with lots of training and
experience in epidemiology have trouble really coming to grips with the
issue on confidence intervals (they seem to end up thinking the
distinction is really one of semantics rather than of probability).
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: CHINNIS: It's all relative
Date: Tue, 08 Mar 2005 06:48:57 -0500
Message-ID: <d0k3jb$8p0$1@reader1.panix.com>
Usually it is absolute risk reduction or increase that an individual
cares about. However the absolute risk reduction often depends on the
initial baseline absolute risk. Medicine often makes the assumption that
the relative risk reduction holds true over a wide range of absolute
risks, which is an argument in favor of reporting that number.
For example, imagine that airbags cut your risk of dying in a car
accident by one-third. Your absolute benefit from airbags then is highly
dependent on your risk of being in a car accident, and this goes up the
more you drive. So someone who drives 20,000 miles a year gets a lot
more benefit from installing airbags than someone who drives 3,000 miles
a year if both have the same risk per mile of an accident. The relative
risk reduction of death in a car accident is 30% for both people but the
absolute risk reduction is different. It's easy to see why people would
be interested in both numbers when thinking about the benefits of
airbags. The absolute risk reduction is important to the individual, and
the relative risk reduction lets the individual calculate the absolute
risk reduction based on his or her baseline risk.
Not all drugs/interventions/actions actually have this nice relationship
between relative and absolute risk reductions over the range of absolute
risks, but some do. Statins (as you might predict in a thread with Zee)
actually seem to. In almost all studies of statins, the relative risk
reduction for cardiac events and cardiac death is around 30%. So it
makes sense if you are thinking of taking a statin to figure out what
your absolute risk is and whether you have any value in dropping that
risk by one third. Most people would not see much value in decreasing
their ten-year risk of cardiac death from 0.3 percent to 0.2 percent by
taking a statin every day, even though it probably would work to do
that. (This is pure extrapolation; no study is likely to ever be able to
show an absolute risk reduction that small.)
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Intensive Lipid Lowering with Atorvastatin
Date: Tue, 08 Mar 2005 19:13:15 -0500
Message-ID: <d0lf6s$f99$1@reader1.panix.com>
Jim Chinnis wrote:
> "Zee" <zwalanga@yahoo.com> wrote in part:
>>Not quite true. Those on the LIPITOR arm had **elevatING** liver
>>enzymes. That's elevatING, not elevated. A VERY good example of just
>>what we have been talking about today. The full text says something
>>slightly different than the abstract. And in the case of statins, that
>>something is VERY significant. ElevatING.
>
>
> You changed my quote (which was from the full text.). The point I
> was addressing was from the earlier thead re cancer rising as
> cholesterol dropped. Here a comparison was made between those with
> LDL in very low ranges against others.
Actually, having spent a good amount of time this afternoon looking at
this study, I don't think the issue is so clear (and I decided, given
the ongoing cancer thread, that I ought to post something about this).
High dose atorvastatin (80 mg daily) decreased cardiovascular events and
cardiovascular deaths by about 20% compared with low dose atorvastatin
(10 mg daily) in this enormous (10,000 patient) secondary prevention
trial. However there was no similar decrease in total mortality
(relative risk was 1.01, I think). Why was there no similar decrease?
Well, the main reason was that there were increased cancer deaths in the
patients getting the higher dose of statins. This did not achieve
statistical significance, but the point estimate of the increase was
about 25%.
Although the spin from the paper was that high dose atorvastatin with a
goal LDL<80 mg/dL is the way to go in secondary prevention, it's really
not so clear now. There was an accompanying editorial (available on the
NEJM web site) that I thought addressed this quite well. We now have
some very interesting data to contend with:
1) High dose atorvastatin clearly saves lives after an acute MI (better
than lower dose pravastatin).
2) Statins save lives in primary prevention and secondary prevention and
in general do not seem to increase cancer deaths even after prolonged
follow-up.
3) In both PROSPER and now TNT (the new trial) there did appear to be an
increased risk of cancer deaths. The results of PROSPER may well have
been a fluke -- they weren't seen in other trials -- but the TNT results
are the only data we have in this sort of secondary prevention in
moderate risk patients using high dose atorvastatin.
I think in light of TNT we need to seriously consider that either high
doses of atorvastatin, or large reductions in LDL, might increase cancer
risk. I'm going to be looking at these and other data more over the next
few days, but I can't say I found these a very reassuring set of results.
Note that nothing about this suggests that statins aren't dramatically
better than placebo in secondary prevention. The issue here is whether
lots of statin is better than a little statin.
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Intensive Lipid Lowering with Atorvastatin
Date: Thu, 10 Mar 2005 06:41:26 -0500
Message-ID: <d0pbt3$prf$2@reader1.panix.com>
William Wagner wrote:
> In article <vknv21dnvaous0lf15fgmrkrdof6m40h8l@4ax.com>,
> Jim Chinnis <jchinnis@SPAMalum.mit.edu> wrote:
>
>>It looks to me that if they had chosen a proper composite endpoint that
>>actually summarized all morbidity and mortality, they would have
>>discovered that 80 mg of atorvastatin was no better than 10 mg.
>>--
>>Jim Chinnis Warrenton, Virginia, USA
>
>
>
> Wasn't 10 Mg of Lipitor as effective as placebo? I thought I read that
> here in SMC.
Do you mean in this study (the TNT trial)? There was no placebo arm, and
ethically they could not have a placebo arm. We already know that
statins decrease mortality in secondary prevention compared with placebo.
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Intensive Lipid Lowering with Atorvastatin
Date: Thu, 10 Mar 2005 20:44:37 -0500
Message-ID: <d0qta2$3sg$1@reader1.panix.com>
Juhana Harju wrote:
> David Rind wrote:
> :: Do you mean in this study (the TNT trial)? There was no placebo arm,
> :: and ethically they could not have a placebo arm. We already know that
> :: statins decrease mortality in secondary prevention compared with
> :: placebo.
> ::
> Do statins decrease all-cause mortality among women over 50 years also?
> Any evidence? I just began to wonder this after seeing the Austrian
> study posted by Sharon.
I don't think this observational study from Austria helps answer the
question at all, but the answer depends in part on what exactly you are
asking.
There is no solid evidence that statins decrease all-cause mortality
when used for primary prevention in women. They decrease cardiovascular
events, but studies have really been too small to answer the question on
mortality. You could potentially argue that a primary prevention study
of statins in women with a placebo arm would be ethical. TNT was a
secondary prevention study, however, and was in both men and women.
Even in secondary prevention, though, the question of mortality in women
hasn't been answered perfectly in the published literature. The main
study that should have been large enough to really provide some insight
into this, the Heart Protection Study, showed a decrease in mortality in
all patients, and reported that for their main subgroup endpoint (major
cardiovascular events) women were just like men, but they did not split
out mortality in women as far as I can tell. (If someone knows of
someplace that the HPS published mortality results in women, I'd be
interested in hearing about it.)
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Intensive Lipid Lowering with Atorvastatin
Date: Thu, 10 Mar 2005 20:35:58 -0500
Message-ID: <d0qsq3$5is$1@reader1.panix.com>
Jim Chinnis wrote:
> Continuing on my soliloquy:
>
> While I am concerned about the composite endpoint and was frustrated by
> LaRosa's statement quoted above, the TNT study was directed at secondary
> prevention. The toll of non-fatal cardiovascular events was high--almost
> certainly much higher than morbidity from cancers and other illnesses.
> So LaRosa's statement is correct within the context of their target
> group of patients.
Well, maybe. You would expect that if there were lots of deaths from
other problems that there was also even more morbidity from those
problems. If, for instance, the 13% increase in cancer deaths was real,
than there was undoubtedly a greater than 13% increase in incident
cancers. Not so clear that you'd prefer cancer morbidity to
cardiovascular morbidity. (Although, in the other direction, stroke was
one of the cardiovascular events.)
--
David Rind
drind@caregroup.harvard.edu
From: Jim Chinnis <jchinnis@SPAMalum.mit.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Intensive Lipid Lowering with Atorvastatin
Message-ID: <23is21prmvqj2d6449i1ngkbgotdgoj2er@4ax.com>
Date: Wed, 09 Mar 2005 02:14:00 GMT
David Rind <drind@caregroup.harvard.edu> wrote in part:
>High dose atorvastatin (80 mg daily) decreased cardiovascular events and
>cardiovascular deaths by about 20% compared with low dose atorvastatin
>(10 mg daily) in this enormous (10,000 patient) secondary prevention
>trial. However there was no similar decrease in total mortality
>(relative risk was 1.01, I think). Why was there no similar decrease?
>Well, the main reason was that there were increased cancer deaths in the
>patients getting the higher dose of statins. This did not achieve
>statistical significance, but the point estimate of the increase was
>about 25%.
>
>Although the spin from the paper was that high dose atorvastatin with a
>goal LDL<80 mg/dL is the way to go in secondary prevention, it's really
>not so clear now. There was an accompanying editorial (available on the
>NEJM web site) that I thought addressed this quite well. We now have
>some very interesting data to contend with:
>
>1) High dose atorvastatin clearly saves lives after an acute MI (better
>than lower dose pravastatin).
>2) Statins save lives in primary prevention and secondary prevention and
>in general do not seem to increase cancer deaths even after prolonged
>follow-up.
>3) In both PROSPER and now TNT (the new trial) there did appear to be an
>increased risk of cancer deaths. The results of PROSPER may well have
>been a fluke -- they weren't seen in other trials -- but the TNT results
>are the only data we have in this sort of secondary prevention in
>moderate risk patients using high dose atorvastatin.
>
>I think in light of TNT we need to seriously consider that either high
>doses of atorvastatin, or large reductions in LDL, might increase cancer
>risk. I'm going to be looking at these and other data more over the next
>few days, but I can't say I found these a very reassuring set of results.
>
>Note that nothing about this suggests that statins aren't dramatically
>better than placebo in secondary prevention. The issue here is whether
>lots of statin is better than a little statin.
Thank you for posting your observations on this. I've have a chaotic day
and have still not had a chance to read the paper through from beginning
to end in one sitting. But I'd like to pose a few issues here--almost
certainly nothing you haven't thought about.
The principal issue for me personally is the question of whether it is
the dose of atorvastatin or the level of LDL that is responsible for
either the inferred benefits or the apparent increase in
non-cardiovascular deaths. More on that shortly.
The cancer mortality hazard ratio is 1.13 and the hazard ratio for
nontraumatic causes other than cancer is 1.35. While the first category
is more common than the second, the difference in hazard ratios more
than makes up for it: the second (non-cancer) category makes up more of
the difference between 10 and 80 mg groups than does the cancer
category.
"No significant increase in adverse events of any type was identified
among patients who had very low levels of LDL cholesterol (less than 70
mg per deciliter [1.8 mmol per liter]), as compared with those with
higher levels." Upon careful reading, that has to mean not the
comparison between 10 and 80 mg of atorvastatin, but between two groups
distinguished by LDL level. I would love to see the data! Does this mean
that the increase in cancer et al. seen with 80 mg atorvastatin vs 10 mg
is NOT seen with <70 mg/dl LDL vs >70? I doubt it. But the data are not
provided and the issue is not discussed. The fact is that the study is
underpowered in terms of mortality, but the contrast between death from
cardiovascular causes (p=.09) and all causes (p=.92) is quite
startling... And this is in what I would call a high (CVD) risk group!
What would the results look like in a lower risk group?! I can imagine a
significant increase in mortality in the 80 mg group. And a large
portion is due to cancer...in a five-year study!
Returning to whether it is the dose of atorvastatin or the level of LDL
that is responsible for either the inferred benefits or the apparent
increase in non-cardiovascular deaths, my personal situation may not be
that unusual now. I am taking 10 mg atorvastatin, mostly because of a
positive calcium score (70th percentile) on a coronary artery EB-CT scan
taken because of family history. I am asymptomatic. But the 10 mg (along
with lifestyle changes) drops my LDL from about 100 to 47, my total
cholesterol from 173 to 121, and my HDL has increased from 42 to 61
(usually even higher now) from lifestyle changes.
So...do I have the benefits of the 80 mg atorvastatin and the
(non-significant...) risks of the 10 mg atorvastatin, or I am just more
like (extrapolated) 160 mg atorvastatin all around?
What a morass...
--
Jim Chinnis Warrenton, Virginia, USA
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Intensive Lipid Lowering with Atorvastatin
Date: Thu, 10 Mar 2005 06:39:22 -0500
Message-ID: <d0pbpd$prf$1@reader1.panix.com>
Jim Chinnis wrote:
> So...do I have the benefits of the 80 mg atorvastatin and the
> (non-significant...) risks of the 10 mg atorvastatin, or I am just more
> like (extrapolated) 160 mg atorvastatin all around?
>
> What a morass...
I agree that this is one of the major questions the study raises.
Hopefully there will be some studies with combination atorvastatin and
ezetimibe published before long that look at what happens when you reach
the same target LDL by two different methods (high dose atorvastatin
versus low dose atorvastatin plus ezetimibe). This may give some added
indication as to whether both benefits and risks are due to the target
LDL or the dose of the atorvastatin.
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Intensive Lipid Lowering with Atorvastatin
Date: Fri, 11 Mar 2005 06:59:09 -0500
Message-ID: <d0s1ag$mar$1@reader1.panix.com>
Jim Chinnis wrote:
> The idea that the extra 70 mg of atorvastatin could *cause* the
> compensatory increase in both cancers and other illnesses seems a bit
> hard to accept, particularly cancer within a five-year period. I'm
> guessing that we are seeing random effects in looking at outcomes that
> the study is underpowered to detect. But it does mean that more data are
> needed.
The problem is that just such an effect has always been the fear with
cholesterol-lowering therapy. Pretty much every study prior to the
statins that looked at primary prevention with a cholesterol-lowering
therapy found no decrease in overall mortality because of an increase in
noncardiac mortality (in various studies, the etiologies were things
such as cancer, trauma, and suicide). Every time this happened people
would say that it seemed unlikely that the therapy could have been
responsible, but it kept happening.
In general, this is not what has been seen in the statin trials (with
the exception of PROSPER). I had always suspected that that was because
the statins are so beneficial on cardiac mortality that even if there
were a small increase in noncardiac mortality it was being overwhelmed.
In TNT, though, it may be that most of the cardiac mortality benefit
already accrues with 10 mg of atorvastatin, so when you compare 80 mg
atorvastatin, noncardiac deaths become enough of an issue to
counterbalance the cardiac mortality benefit.
It might just be a statistical fluke, but it's easy to make an argument
based on prior studies that we should be quite concerned by this result.
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Intensive Lipid Lowering with Atorvastatin
Date: Fri, 11 Mar 2005 07:07:58 -0500
Message-ID: <d0s1qr$ok3$1@reader1.panix.com>
Juhana Harju wrote:
> As low HDL and high triglyserides have been established as the best risk
> factors among post-menopausal women in several studies, wouldn't it be
> the best policy to try to increase HDL and decrease triglyserides
> instead of lowering LDL cholesterol by statins? After all, total
> cholesterol and LDL are not good indicators of cardiovascular mortality
> in post-menopausal women.
Not necessarily. Personally, I worry a lot about making the leap from
markers of risk to targets for therapy. People (including cardiac
researchers) do this all the time, but that doesn't make it reasonable.
We know that statins decrease cardiovascular mortality. This may or may
not be due to the fact that they decrease LDL cholesterol. For instance,
we do not know that reducing homocysteine levels or CRP decreases
cardiac mortality even though they are risk factors for cardiac events.
It's a complex subject. It seems reasonable that if X is a risk factor
than lowering X must be good, but this isn't always the case. X may be a
risk factor just because it's a marker for some other process and
lowering it may be useless or even harmful. It may turn out that drugs
to increase HDL will be beneficial, but studies proving it are needed.
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Intensive Lipid Lowering with Atorvastatin
Date: Thu, 17 Mar 2005 20:47:43 -0500
Message-ID: <d1dc3j$3pt$1@reader1.panix.com>
David Rind wrote:
> Juhana Harju wrote:
>
>> David Rind wrote:
>
>
>> :: Do you mean in this study (the TNT trial)? There was no placebo arm,
>> :: and ethically they could not have a placebo arm. We already know that
>> :: statins decrease mortality in secondary prevention compared with
>> :: placebo.
>> ::
>
>
>> Do statins decrease all-cause mortality among women over 50 years also?
>> Any evidence? I just began to wonder this after seeing the Austrian
>> study posted by Sharon.
>
>
> I don't think this observational study from Austria helps answer the
> question at all, but the answer depends in part on what exactly you are
> asking.
>
> There is no solid evidence that statins decrease all-cause mortality
> when used for primary prevention in women. They decrease cardiovascular
> events, but studies have really been too small to answer the question on
> mortality. You could potentially argue that a primary prevention study
> of statins in women with a placebo arm would be ethical. TNT was a
> secondary prevention study, however, and was in both men and women.
>
> Even in secondary prevention, though, the question of mortality in women
> hasn't been answered perfectly in the published literature. The main
> study that should have been large enough to really provide some insight
> into this, the Heart Protection Study, showed a decrease in mortality in
> all patients, and reported that for their main subgroup endpoint (major
> cardiovascular events) women were just like men, but they did not split
> out mortality in women as far as I can tell. (If someone knows of
> someplace that the HPS published mortality results in women, I'd be
> interested in hearing about it.)
So, to reply to my own post a week or so later: the HPS group published
its data on mortality by subgroups in BMC Medicine yesterday.
Reassuringly, treatment decreased all-cause mortality in the various
subgroups of interest including women, the elderly, and people who
started with low LDL-C levels. There did not seem to be any increase in
noncardiac mortality.
--
David Rind
drind@caregroup.harvard.edu
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: alt.support.alzheimers,sci.med,misc.health.arthritis
Subject: Re: pharmacists on statins
Date: 29 Apr 2005 15:38:29 -0700
Message-ID: <1114814309.695941.228810@o13g2000cwo.googlegroups.com>
>>Physicians know that lifesaving drugs like penicillin can sometimes
cause life-threatening reactions. It's time to recognize that even
great drugs like statins can cause some people serious harm. <<
They can indeed, but it's idiosyncratic. It seems unlikely that most
side effects result from the statin's main effect of inhibiting HMG-CoA
reductase. For they vary from person to person, and from one drug in
this class to the next. You just have to each one, and watch carefully
each time a new person and a new statin are introduced.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med,sci.med.pharmacy
Subject: Re: Statins help prevent breast cancer, study finds
Date: 20 May 2005 17:15:46 -0700
Message-ID: <1116634546.421942.261390@g14g2000cwa.googlegroups.com>
>>I'm very willing to hear your explanation of how this statement
"statins cause cancer" is wrong. <<
COMMENT:
If you qualify it by noting that statins cause cancer in cancer-prone
rodents, I have no problem with it. In the human trials, the meta
analyses show nothing. It's a huge amount of data. PROSPER's the only
trial where there's been an statistically significant increase of
cancer seen, and if you're going to look at the p = 0.05 level, you're
likely to have one trial in 20 show a statistically significant
increase (and one that shows a decrease) just by chance. That's about
where we are with statins.
As I've said before, there's a lot better evidence that FIBRATES and
cholesterol binding resins cause cancer in humans, and no evidence at
all that they save lives, and scant evidence that they even decrease
MI's much. They are examples of lousy pharmaceuticals that exist to
treat numbers. I personally think they ought to be outlawed, but
they've managed to make it to the generic stage (most of them-- Tricor
being an exception) where nobody cares anymore, and people figure
anything that's been around as long as cholestyramine has to work, or
it wouldn't have been around so long. So it's hard getting rid of them.
But if we're going to start getting rid of bad cardiology drugs, lets
start with the worst first, and that would be those. By that time, the
statins will have proven themselves one way or the other. I think
statins will have a place in the care of people who have bad coronary
disease for a long time.
You've heard me expound before on Louis Goodman's 3 stages of drug
development. Nearly all drugs go through them. First is the Panacea
Phase, where we think the hot new drug should be in the water supply.
Next comes the Pandora Plague Phase, where we learn about odd and rare
side effects, and it looks like the worst mistake the pharm companies
ever made. Finally, all drugs come (usually about the time they get to
be generic) to the Perfectly Pedestrian Pharmaceutical Phase. You know
who to give them to, and who not to, like acutane and AZT and metformin
and Paxil. In some people they are very useful, and in some people they
can be very bad. The practice of medicine takes wisdom. And practice.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med,sci.med.pharmacy
Subject: Re: Statins help prevent breast cancer, study finds
Date: 20 May 2005 17:47:15 -0700
Message-ID: <1116636435.850997.113560@g44g2000cwa.googlegroups.com>
>>Right. So now that I have some kind of life-destroying metabolic
myopathy triggered by sttains, would you give them to me? <<
COMMENT:
Probably not :)
<<My endocrinologist would. <<
No comment.
>>My g.p. wouldn't. In fact, since I have so obviously had an adverse
reaction to statins that has lasted beyond the two-week washout
promised by Bayer, she won't see me. She's scared (said our mutual
friend the head of our city's largest hospital ICU). So is the sports
medicine specialist she tried to fob me off on; when I demurred about
the statin he wanted to give me, he sat back, folded his arms and said,
"I'm very worried about you. Very worried." Then he told me he wasn't
taking new patients.
I don't have anyone to practise on me anymore. I think I may be better
off. <<
Possible. There are patients born in every age who have something the
doctors of that age are treating exactly wrongly. It happens. I don't
think it's common, but it happens.
>>So see Steve, in spite of the fact that I think you are a one hot damn
writer, I don't like the way you practise medicine.<<
What, you mean by statistics? Since nobody has written a textbook on
your personally, that's sort of how we doctors are forced to do it.
>> In a few years,
I'll die of some cardiovascular related thingey, because I can't move
without a flare up of this glycogen storage disorder that's been
triggered.<<
Maybe not. I don't think the high dose fish oil is going to do
something odd to you that we don't know about. It's been pretty well
tested as a drug. They'd be a lot of dead Eskimos and Japanese if not.
>>I guess I'm lucky I'm not dead from the Tricor. Is that what you're
saying? <<
Tricor sucks as a preventive, but the total excess cancer risk is mild.
So no, it's expected that you're not dead. But don't expect the stuff
do to more than deplete your wallet. I would suggest 20 or 30 grams of
fishoil a day instead. It will do everything Tricor will to your
triglycerides, and may save your life also.
And the nice colored Mediterranean diet is not a bad idea, either.
Berries, pomegranites, grapes, fresh produce in all colors, red wine,
olives, chocolate. I don't know if it will save your life, but what you
have left of it, will certainly be better.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: statins do not save lives
Date: 15 May 2005 21:32:10 -0700
Message-ID: <1116217930.219206.111340@g44g2000cwa.googlegroups.com>
>>Women please note:
"...no statin trials with even the slightest hint
of a mortality benefit in women (JAMA, JACC, BMJ)
and women should be told so in the guidelines."
E. Vos<<
COMMENT:
Somehow the essential caveat got missed that although there are no
purely PRIMARY prevention statin trials with mortality benefits in
women, you can't say that about secondary prevention in women. Women
did experience a significant *total* decrease in mortality in the 4S
trial, as did every other group in that trial. The total mortality
(women plus men) was 12% in the placebo vs. 8% in the simvastatin group
over 5.4 years median followup, for a decrease of 30% in chance of
dying. For women it was less, but still significantly lower. Of
course, many of the 4444 participants in the 4S trial had heart disease
and knew it.
But there are some women with heart disease who will read the "no
statin benefits for women" line in the article above, and think it
applies to them. It doesn't. Simvastatin significantly decreases risk
of dying for all causes, in this group (women with heart disease and
high cholesterol). It's outragious to shade the facts so as to (by
implication) suggest otherwise.
I'm also annoyed at the cancer increase in the PROSPER trial being
mentioned again and again. From what I can tell, it's an abberation. No
other statin trial has seen anything like it. Even the 4S trial when
run out open label beyond 10 years (with most of the former placebo
group naturally deciding to switch to simvastatin) had a lower cancer
mortality after 10 years in the simvastatin group. And total mortality
was STILL 414 deaths in the initial statin group vs 468 in the initial
placebo group (many of which had been on statins by this time for half
the time).
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: statins do not save lives
Date: 16 May 2005 23:14:43 -0700
Message-ID: <1116310483.024164.3380@o13g2000cwo.googlegroups.com>
>>The rate of serious statin side effects is far higher than the risk of
CAD in low-risk and moderate risk women. .... Also, the total range of
choices for increasing heart health is not exhausted by "statins or
death." <<
COMMENT:
Well, you'd think it was, giving how you insist on focusing on
mortality.
But we're not talking about low and moderate risk women. This thread
didn't start out qualifying any group of women. The toral risk of major
coronary events in the 4S trial in women was 160 in 827 high risk women
over 5 years, which is 19%. That's high, and statins prevented about a
third of them. That's in line with other trial results. So what major
side effect can you expect from simvastatin which is as serious as a
heart attack, and that you can expect at least 7% chance of getting, in
5 years? Since for these women something like 7 in 100 would have a
heart attack in the next 5 years, preventable by a statin. That's your
benefit. Now, what's the risk which outweighs that? And who says so,
and cite the study.
SBH
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: response from Eddie Vos: statins do not save lives
Date: Mon, 16 May 2005 21:14:51 -0400
Message-ID: <d6bgen$de8$1@reader1.panix.com>
outrider wrote:
> The following response to Dr. Harris came to me from Eddie Vos.
>
> Dr. Harris makes two points: 4S and PROSPER.
>
> 1. 4S: Dr. Harris misrepresents 4S where in fact there was a 16%
> INCREASE in female deaths (p=0.58) with 3 fewer CHD offset by 6 more
> non-CHD deaths on simvastatin: Table 3 in
> http://circ.ahajournals.org/cgi/content/full/96/12/4211 or /T3 . If NOT
> lowering deaths is success from putting half of 827 women with heart
> disease on statin for 5 years, I would question Dr. Harris' criteria for
> success. Clearly, this is a failure of therapy especially since there
> there are zero trials or meta analysis showing that statins could
> possibly extend the lives of women qualifying for trials. From JAMA 2004
> Medline 15138247: "For women with known cardiovascular disease,
> treatment of hyperlipidemia ... does not affect total mortality." Can
> data from 20,000 women in trials over 1 year in duration be all wrong?
>
> A more serious shadow over 4S is the likelihood of sponsor run data
> management misclassification of patients, as they admitted in the text
> of Table 3 above to misclassifying a female as a male statin death.
> NOTHING happens in the mortality curves for ~1.5 years; then placebo
> starts dying at an increased and statin at a decreased rate, a never
> explained phenomenon that inexplicably reverses during the study-end
> follow up period, with original statin patients starting to die at a
> relative increased rate!
>
> 2. Dr. Harris may be annoyed hearing about PROSPER's significant
> increase in 'new' cancers in the statin group with fewer smokers, but
> data are data. There is a glimpse as to cause in the response letters
> published in Lancet and there are indeed many pathways by which statins
> may promote cancer: reduced CoQ10, squalene, cholesterol,
> farnesyl(ation) et al, angiogenesis in 'dormant' cancer nodes, and
> whoknows, and as per most animal studies.
>
> The PROSPER authors meta-analysed away their cancer mortality increase
> (not smoking and group size adjusted not quite 'significant') by
> comparing with trials in younger patients. Similarly, smoking for 5
> years in younger groups may not reveal a carcinogenic effect from
> tobacco. PROSPER is important because its rationale was to establish
> all-cause effects in older people and there was zero mortality benefit
> in this high risk group.
>
> Dr. Harris cavalierly dismisses increased cancer deaths in PROSPER as an
> 'aberration' but what about the 'first do no harm' concept? One letter
> writer about PROSPER in Lancet said: it changed the way people died,
> from heart disease to cancer. Given the choice at age 80, about the mean
> age of death in PROSPER, to die in the same week of cancer or heart
> attack, please give me the latter. Few cardiologists putting people on
> statin would disagree with this for themselves I'd imagine, and older
> patients and women of any age should be informed of these study
> results.
>
> For those interested in mortality and statins, may I refer to
> http://www.health-heart.org/cholesterol.htm with the J-LIT trial being
> ominous, showing significant 2-4 times greater mortality in
> 'hyper-responders' to simvastatin in this massive 6 year observational
> study in hypercholesterolemic Japanese, 2/3rds women and most deaths
> from cancer.
>
> Eddie Vos vos@health-heart.org
When this issue came up a few months, I pointed out that the study that
could definitively answer the question was the enormous Heart Protection
Study (HPS). At the time, HPS had not published the relevant subgroup
analyses to really know what was going on with various causes of
mortality in various subgroups. However, as I mentioned a month or two
ago, HPS soon after that did publish these results:
The effects of cholesterol lowering with simvastatin on cause-specific
mortality and on cancer incidence in 20,536 high-risk people: a
randomised placebo-controlled trial [ISRCTN48489393]
Heart Protection Study Collaborative Group
Heart Protection Study, Clinical Trial Service Unit & Epidemiological
Studies Unit, Harkness Building, Radcliffe Infirmary, Oxford OX2 6HE, UK
BMC Medicine 2005, 3:6 doi:10.1186/1741-7015-3-6
You can go to www.biomedcentral.com, sign up, and read the article for
free. It shows that women benefit in cardiac mortality with no hint of
an increase in noncardiac mortality. Also, the elderly benefit. Also,
there was no evidence of an increase in cancer deaths. Statins are
clearly beneficial in secondary prevention in women and the benefits
look just like those in men (same relative reduction in mortality).
There is no reason to expect that this same relationship would not hold
up in primary prevention, however the absolute risk in most women is so
small that treatment for primary prevention will not be of much absolute
benefit in many women.
--
David Rind
drind@caregroup.harvard.edu
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: response from Eddie Vos: statins do not save lives
Date: 16 May 2005 23:30:03 -0700
Message-ID: <1116311403.573486.318040@g49g2000cwa.googlegroups.com>
The following response to Dr. Harris came to me from Eddie Vos.
Dr. Harris makes two points: 4S and PROSPER.
>> 1. 4S: Dr. Harris misrepresents 4S where in fact there was a
16% INCREASE in female deaths (p=3D0.58) with 3 fewer CHD offset by 6
more non-CHD deaths on simvastatin: Table 3 in
http://circ.ahajournals.org/cg=ADi/content/full/96/12/4211 or /T3 . If
NOT lowering deaths is success from putting half of 827 women with heart
disease on statin for 5 years, I would question Dr. Harris' criteria for
success.<<
COMMENT:
You've got me, as I misread the MI data for mortality data. The 4S is
underpowered for women's deaths, since it has 4.3 times the number of
men, and these men had 7.4 times the number of deaths. There were only
52 deaths in the women, and they broke out as 27 statin/25 placebo (not
significant). However, the MI's in women were significantly less (by
about a third) very similar to the results in men. There's every reason
to think that a study adequately powered to look at female mortality in
statins will show the same result as for men, and as Dr. Rind points
out, the HPS is showing just that.
My criteria for success? Those 7 women in every 100 who don't have the
MI in 5 years, if they take a statin. Having a heart attack is a slight
inconvenience. May I see your statistics that suggest that 7% of women
who take statins will suffer some side effect which is worse than a
heart attack? Even if we didn't have the HPS data on mortality?
>>A more serious shadow over 4S is the likelihood of sponsor run data
management misclassification of patients, as they admitted in the text
of Table 3 above to misclassifying a female as a male statin death. <<
Did it change the significance of the result?
>>NOTHING happens in the mortality curves for ~1.5 years; then placebo
starts dying at an increased and statin at a decreased rate, a never
explained phenomenon that inexplicably reverses during the study-end
follow up period, with original statin patients starting to die at a
relative increased rate! <<
Well, with small numbers of events you're going to have to expect such
fluxuations. Roll of the dice. Take two groups of dice rollers and they
will always have "inexplicable" departures from and returns to each
other, with one side winning and now the other. All this means is that
a bigger study is needed.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: response from Eddie Vos: statins do not save lives
Date: 16 May 2005 23:44:27 -0700
Message-ID: <1116312267.606757.240070@g44g2000cwa.googlegroups.com>
>>2. Dr. Harris may be annoyed hearing about PROSPER's significant
increase in 'new' cancers in the statin group with fewer smokers, but
data are data. <<
Yes, they are, but with much larger studies than PROSPER showing no
such effects, and meta-analyses also, the PROSPER results are hard to
explain. Perhaps statins should not be given to people over 70, until
other studies have had a chance to break out groups similar to those in
PROSPER, to see if the subgroup effect is robust.
>>Dr. Harris cavalierly dismisses increased cancer deaths in PROSPER as
an 'aberration' but what about the 'first do no harm' concept? <<
If taken literally, it would prevent recommendations for many types of
exercise. Exercise is not benign. Some types of exercise increase
quality of life, but haven't been shown to decrease mortality. Perhaps
you don't die of a heart attack, but you do break a hip or get hit by a
car. Life is tradeoffs. There's nothing wrong with tradeoffs so long as
they are informed ones.
>>One letter writer about PROSPER in Lancet said: it changed the way
people died, from heart disease to cancer. Given the choice at age 80,
about the mean age of death in PROSPER, to die in the same week of
cancer or heart attack, please give me the latter. <<
You're assuming sudden death and not the long drawn-out death of the
cardiac cripple with congestive failure. In any case, the comparison is
pointless until we find out if the cancer increase in this study is
real. No other human study suggests that it is. I think odds are good
that it's not. Statin cancer in lab animals is rodent liver cancer,
mostly. Not really relevent to humans.
>>For those interested in mortality and statins, may I refer to
http://www.health-heart.org/ch=ADolesterol.htm with the J-LIT trial
being ominous, showing significant 2-4 times greater mortality in
'hyper-responders' to simvastatin in this massive 6 year observational
study in hypercholesterolemic Japanese, 2/3rds women and most deaths
from cancer. <<
COMMENT:
Cancer itself greatly lowers cholesterol, so I'm not surprised that
women with occult cancers had greater cholesterol drops with a statin.
This is not a controlled study. It's interesting, but says nothing
about cause and effect. At best, it suggests that you should take a
harder look at your great "statin successes" and perhaps screen them
for occult GI cancers that you'd missed.
SBH
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: response from Eddie Vos: statins do not save lives
Date: Tue, 17 May 2005 21:42:13 -0400
Message-ID: <d6e6e1$194$1@reader1.panix.com>
Steve Harris wrote:
> >>2. Dr. Harris may be annoyed hearing about PROSPER's significant
> increase in 'new' cancers in the statin group with fewer smokers, but
> data are data. <<
>
>
> Yes, they are, but with much larger studies than PROSPER showing no
> such effects, and meta-analyses also, the PROSPER results are hard to
> explain. Perhaps statins should not be given to people over 70, until
> other studies have had a chance to break out groups similar to those in
> PROSPER, to see if the subgroup effect is robust.
Lots of other studies have done so at this point. A meta-analysis of
statins in the elderly (published as part of PROSPER, if I recall
correctly) showed no evidence of increased cancer with statins in the
elderly. HPS, published later, had plenty of elderly patients and also
showed no such increase. The PROSPER results look like they were a
fluke. That said, TNT had a nonsignificant 13% increase in cancer
mortality in the high dose arm -- though this may be explained by the
"people have to die of something" argument. (Note, the 25% increase in
noncardiac mortality in TNT leading to no reduction in all-cause
mortality cannot be explained away by the same argument. It may also
have been a statistical fluke or it may be evidence of a problem.)
--
David Rind
drind@caregroup.harvard.edu
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: VOS to Dr. RIND: statins do not save lives
Date: 20 May 2005 19:16:16 -0700
Message-ID: <1116641776.314649.128190@o13g2000cwo.googlegroups.com>
>>Then, same statin in a larger trial TexCAPS/AFCAPS: 3 MORE dead on
statin at study end and, guess what, again 40% MORE cancer. <<
COMMENT:
Which wasn't statistically significant (P was 0.13 as the confidence
limits were 0.91 and 2.19).
I do have to second your point that this particular trial had a pretty
funny interpretation given that it ended up with 80 people dead on
Lovastatin after 5 years against 77 on placebo, and hailed it as a
major breakthrough because the cardiac EVENTS were statistically
significant, but the cancer events weren't. Basically, the drug did
nothing but cost money, in terms of saving lives. They should therefore
have analyzed it by quality of life to see if intension to treat was a
reasonable idea. They didn't.
Still, as regards cancer, the bottom line is that if you put all these
studies together, excess cancer in statin trials doesn't even have a
trend toward significance. It's as unfair to cherrypick trials in which
cancer trends are up, as it is to pick those in which they are down.
Here's a meta analysis of the cancer data from the 5 largest randomized
prospective statin trials combined. Cancer result: zip. Not a trend in
any direction.
Am J Med. 2001 Jun 15;110(9):716-23.
Comment in:
Am J Med. 2001 Jun 15;110(9):738-40.
Am J Med. 2002 Feb 1;112(2):157-8.
Do statins cause cancer? A meta-analysis of large randomized clinical
trials.
Bjerre LM, LeLorier J.
Department of Epidemiology and Biostatistics, McGill University,
Montreal, Quebec, Canada.
PURPOSE: Although the short-term safety and tolerability of statins has
been well established, their potential carcinogenicity in the long term
is still debated. The goal of this study was to determine whether
long-term treatment with statins is associated with an increased risk of
fatal and nonfatal cancers. METHODS: We searched the Medline database
between January 1966 and December 1999 for randomized, controlled trials
of human subjects in which monotherapy with a statin was compared with
placebo. No language restrictions were applied. Only trials with a
minimum treatment duration of 4 years and a minimum of 1,000 subjects
were included. Studies that did not provide information on fatal or
nonfatal cancers were excluded. Data on fatal and nonfatal cancers and
all-cause mortality were extracted by a single nonblinded reviewer.
Overall crude estimates of risk difference were computed by summing the
numerators and denominators of trial-specific risk estimates. RESULTS:
Five trials met the inclusion criteria. The estimated differences in
absolute risk between treatment and placebo were as follows (negative
risks indicate that treatment was safer than placebo): all nonfatal
cancers, 0.0% (95% confidence interval [CI]: -0.8% to 0.8%); all fatal
cancers, -0.1% (95% CI: -0.7% to 0.4%); all fatal and nonfatal cancers
combined, -0.1% (95% CI: -1.0% to 0.7%); and all-cause mortality, -1.5%
(95% CI: 2.8% to 0.2%). CONCLUSION: This study demonstrates no
association between statin use over a 5-year period and the risk of fatal
and nonfatal cancers. This conclusion is limited by the relatively short
follow-up of the studies analyzed. Similar analyses of data from studies
with longer follow-up periods would be valuable.
Publication Types:
Meta-Analysis
PMID: 11403756 [PubMed - indexed for MEDLINE]
SBH
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: VOS to Dr. RIND: statins do not save lives
Date: Sat, 21 May 2005 18:20:02 -0400
Message-ID: <d6oc31$d8q$1@reader1.panix.com>
outrider wrote:
> James Wright of Therapeutics Initiative requested *all* negative
> results from the HPS trial for his evidence based analysis of statins
> in secondary prevention. He has yet to receive them. Is this acceptable
> to you David?
>
> http://www.ti.ubc.ca/pages/letter49.htm
> "Total serious adverse events were not reported."
>
> And:
>
> "HPS was unusual in having a pre-randomization period in which 32,145
> recruited patients were treated with simvastatin 40 mg for 4 to 6
> weeks. Thirty six percent (11,609) of these patients were dropped from
> the study for various reasons: poor compliance, patient choice, side
> effects, etc. Because large numbers of problematic patients were
> excluded, the HPS results cannot be used to predict the safety and
> tolerance of simvastatin in the general population."
>
> Is *this* acceptable to you David?
>
> Zee
I'm not clear on question one. If I have more time later, I'll take a
look at the web page, but it's not like HPS is just going to give their
raw data to whomever asks -- they're still getting publications out of it.
On question two, it depends what you mean. I agree that run in periods
in trials affect the generalizability of the results. In this particular
case I'm not particularly worried that it affects the mortality results,
but I'm sure that it makes statins look more tolerable than they really
are. The general experience of clinicians is that patients have a lot
higher rate of side effects (mainly muscle pain) on statins than you
would expect from reading the clinical trials. Run in periods like this
are one cause of the discrepancy. (Even without run in periods, people
who participate in clinical trials routinely seem to do better and have
fewer side effects than the general population of patients.)
--
David Rind
drind@caregroup.harvard.edu
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med
Subject: Re: Question about Chol. medications
Date: 3 Jun 2005 16:58:33 -0700
Message-ID: <1117843113.092201.18170@o13g2000cwo.googlegroups.com>
>>I am presently taking a Pravachol which is a statin medication to
control cholesterol. I have some muscle pain and joint pain. I recently
found out that statin medications cause some people to develop
Rhabdomyolysis. Are there any medications other than statin medications
that can be used to control cholesterol? <<
COMMENT:
You can get muscle and joint pain from these drugs whether you have
rhabdomyolysis or not. The only way to see is stop them. Talk to your
doc and be firm. But don't worry. Once people start on these things,
they think it's like they're being kept alive by them. Wrong. It's not
likely you're going to fall over on your face and die if you take a
drug holiday from a statin. People treat these things like beta
blockers that you dare not stop all at once. Well, they're not like
that at all. And they aren't worth having ANY side effects from.
SBH
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Wht I'd Like from This Group
Date: Sun, 12 Jun 2005 09:16:54 -0400
Message-ID: <d8hcgi$q21$1@reader1.panix.com>
Rita wrote:
> I see the battle of the statins absorbing all the
> bandwidth in this group. Which is not terribly
> helpful for one who wishes to lower her cholesterol
> without statins.
>
> I'd like to learn about specific eating plans people
> have used to lower their cholesterol without statins.
> If anyone here hss managed to do so. Detail, details,
> how did you go about it? What foods do you absolutely
> avoid and which have you added?
>
> Assuming it can be done, that is, to significantly
> lower cholesterol without statins, how have you folks
> gone about it? And how successful have you been?
It depends some on how high the cholesterol level is and why it needs to
be lowered. Very few people are able to stick with a diet that can lower
cholesterol levels to the degree that statins accomplish. For instance,
extreme low fat diets can achieve these sorts of reductions in some
people, but very few people in the US will tolerate such a diet.
Furthermore, if the reason to lower cholesterol is because someone has
known coronary heart disease, it's not clear that all the benefit of
statins can be achieved simply by lowering cholesterol levels by some
other method. Statins appear likely to have other effects that are
important in this situation.
Also, lots of people seem to believe that it is really important to
lower their cholesterol levels, when the actual benefit to be expected
is minimal. If, for instance, someone who has a high cholesterol level
and a 10-year risk of a cardiac event of 3 percent (as might be the case
in a lot of people with a high cholesterol level), reducing the
cholesterol level with a statin would likely decrease that 10-year risk
to about 2 percent. Reducing it with diet would probably not even
decrease the risk by this much. (This is not to suggest that reducing
cholesterol levels is never important -- people with higher risks of
cardiac events can expect much greater risk reductions with statins and
perhaps with other methods of lowering cholesterol.)
--
David Rind
drind@caregroup.harvard.edu
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: statins don't reduce dementia risk
Date: 21 Jul 2005 21:15:53 -0700
Message-ID: <1122005753.545592.40120@g14g2000cwa.googlegroups.com>
mcole8883@yahoo.com wrote:
> With all this talk of memory problems I would like to say that for
> people afraid of this but in dire need of cholesterol reduction they
> should consider pravastatin over zocor or lipitor because it is a
> hydrophilic statin which does not cross the blood brain barrier as do
> the lipophilic statins like lipitor or zocor.
>
> Mike C.
COMMENT:
Pravachol is my favorite statin. However, although it is true that
pravastatin/Pravachol is hydrophilic and therefore the "cleanest" of
the statins, affecting mainly the liver and failing to get into other
tissues well (especially the brain), it is ALSO true that
atorvastatin/Lipitor doesn't particularly get into the brain well,
either.
Thus, it is especially strange to see Lipitor accused particularly of
being the "Thief of Memory" and all the cognitive effects--- effects
which you'd expect of simvastatin/Zocor, out of all the statins. Zocor
DOES get into the brain. If *Zocor* were the one with all the cognitive
problem reports, the whole thing would make a much better story.
1: J Nutr Health Aging. 2002;6(5):324-31.
HMG-CoA reductase inhibitors (statins) in the treatment of Alzheimer's
disease and why it would be ill-advise to use one that crosses the
blood-brain barrier.
Sparks DL, Connor DJ, Browne PJ, Lopez JE, Sabbagh MN.
D. Larry Sparks, Sun Health Research Institute, 10515 W. Santa Fe
Drive, Sun City, Az 85351, USA. E-mail: Larry.Sparks@SunHealth.org
Increased circulating cholesterol has been long linked to an increased
risk of coronary artery disease (CAD), and is now linked to an
increased risk of developing Alzheimer s disease (AD). We first showed
the neuropathologic link between CAD and AD as increased incidence of
cerebral senile plaques in both disorders. We then showed that AD-like
neuropathology occurred in the brains of cholesterol-fed rabbits;
including increased -amyloid (Ab). Currently there are
a number of transgenic mouse models of AD that exhibit enhanced Ab
pathology if cholesterol diet is administered. Culture studies clearly
show that excess cholesterol enhances beta-metabolism of amyloid
precursor protein (APP) and production of -amyloidogenic peptides, and
that sufficiently reducing cholesterol levels by inhibition of
synthesis completely inhibits all beta-metabolism of APP. Our finding
that the elevated levels of Ab in rabbits fed cholesterol diet could be
cleared from the brain by resuming a control diet prompted the
hypothesis that lowering cholesterol levels in the blood of AD
patients may be of some clinical benefit. Pilot data suggests that
therapeutically lowering circulating cholesterol may attenuate Ab
production in the cholesterol-fed rabbit brain, may stabilize cognitive
performance in mildly impaired AD patients, and may reduce the risk of
developing AD. Accordingly, we have initiated a double-blind treatment
trial evaluating Atorvastatin Na+ among 120 mild-to-moderately impaired
AD subjects randomized to one of two groups receiving placebo or active
drug once a day. Atorvastatin is one of a general
class of HMG-CoA reductase inhibitor drugs called statins that lower
cholesterol by inhibition of synthesis. We chose to use Atorvastatin in
this AD Treatment Trial because it does not cross the
blood-brain-barrier, and believe it would be ill-advised to use a
statin that does. This position stems from the observations that excess
cholesterol inhibits cholesterol synthesis and increases Ab production,
that Ab kills cells in part by inhibiting cholesterol synthesis, and
that statins acting at the neuronal level could further exacerbate
degeneration in AD by further inhibition of necessary cholesterol
synthesis.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 12474023 [PubMed - in process]
=====================
2: Clin Pharmacokinet. 1994 Aug;27(2):94-103.
Clinical pharmacokinetics of pravastatin.
Quion JA, Jones PH.
Methodist Hospital/Baylor College of Medicine, Houston, Texas.
The hypolipidaemic agent pravastatin differs from other US Food and Drug
Administration (FDA)-approved HMG-CoA reductase inhibitors (e.g.
lovastatin and simvastatin) because it has greater hydrophilicity, as a
result of the hydroxyl group attached to its decalin ring. The
hydrophilic nature of pravastatin accounts for its minimal penetration
into the intracellular space of nonhepatic tissues, including an apparent
inability to cross the blood-brain barrier. The drug is also well
tolerated because it is rapidly absorbed and excreted, and does not
accumulate in plasma even with repeated administration. Pravastatin is
taken up into the liver by an active transport carrier system, and the
hepatic extraction ratio is high (0.66). The drug and its metabolites are
cleared through both hepatic and renal routes (53 and 47%, respectively).
The dual route of elimination reduces the need for dosage adjustment if
the function of either of these organs is impaired. Dosage adjustments
are also not required on the basis of age or gender. Furthermore, the
drug can be given without regard to food intake, an important
consideration for compliance since lipid-lowering therapy is generally
required long term. The drug is approximately 50% protein bound, and,
therefore, compared with other members of its class the tendency for
displacement of highly protein bound drugs such as warfarin is decreased.
This minimal potential for drug-drug interactions is important for
patients who are taking multiple drugs because of concomitant medical
problems. However, as with any HMG-CoA reductase inhibitor, caution
should be exercised when pravastatin is given with nicotinic acid
(niacin), gemfibrozil or cyclosporin, because of increased risk for
myopathy in patients receiving combination therapy.
Publication Types:
Review
Review, Tutorial
PMID: 7955780 [PubMed - indexed for MEDLINE]
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med,misc.health.diabetes
Subject: Re: cholesterol drugs may harm ill diabetecs
Date: 21 Jul 2005 21:24:24 -0700
Message-ID: <1122006264.242124.225740@g44g2000cwa.googlegroups.com>
David Rind wrote:
> zee wrote:
> > www.nejm.org
> > cholesterol drugs may harm ill diabetics
> >
>
> I don't actually think that's the best interpretation of the study. As I
> pointed out in a post a few months ago when someone claimed that an
> observational study suggested that statins helped patients on dialysis,
> there had just been a presentation of a randomized trial showing the
> opposite. I'm pretty sure this is that study, now published.
>
> I think a more likely interpretation is that statins don't appear to
> help people on dialysis. Calling diabetics on dialysis "ill diabetics"
> is like calling people with metastatic cancer and hypertension "ill
> hypertensives". It kind of misses the point.
COMMENT:
For sure. If you will allow me another metaphor: if you're on a
ventilator in an ICU due to COPD, you're an "ill smoker," but the horse
is out of the barn. Your main problem is organ failure and all the
technology keeping you alive and also invading your body. By that time,
your smoking history is becoming less and less relevent, and Nicorette
patches are not going to help you much.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,sci.med.cardiology,sci.med.pharmacy,misc.health.diabetes
Subject: Re: study: statins may induce neuronal apoptosis
Date: 22 Jul 2005 19:11:10 -0700
Message-ID: <1122084670.746455.128490@g49g2000cwa.googlegroups.com>
Jim Chinnis wrote:
> >At higher doses, however, statins may also inhibit neurite
> >sprouting and even induce neuronal apoptosis.
COMMENT
LOL. In a dish.
Spare me from studies of drug toxicity on neurons in dishes. Some
statins may be able to cross the blood brain barrier, but the ones that
are the worst targets of the hue and cry, don't. Dumping them on naked
neurons in dishes is not likely to advance our scientic understanding.
Unless you, the Lipitor-damaged patient, by some incredble series of
events happen to have had an intrathecal pump delivering a sterile
injectiable solution of Lipitor through a hole in your skull and
directly into the ventricles of your brain and onto your neurons, these
findings **don't apply to you.** Sheesh.
Maybe if we explained this to these guys in German?
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med,sci.med.pharmacy
Subject: Re: statins don't reduce dementia risk
Date: 23 Jul 2005 13:16:06 -0700
Message-ID: <1122149766.607422.270010@f14g2000cwb.googlegroups.com>
Bill wrote:
> "Sharon Hope" <shope@anet.net> wrote in message
> news:WsGdnVS61eA9L3zfRVn-qA@comcast.com...
> > Steve,
> >
> > The brain can be damaged without a drug crossing the blood-brain barrier.
> >
> > Nothing I have read indicates that Lipitor crosses it, yet there is a
> > convincing body of evidence that demonstrates Lipitor causes cognitive
> > damage. Pfizer lists amnesia on the PI.
> >
>
> That is a gross distortion of what it says. All it says is that it happened in
> less than 2% in of the people who underwent trials. It does not say the %. And
> it specificially says that no cause and effect is implied. It is just listed
> as something that happened to less than 2% of the people in trials.
>
> Bill
COMMENT:
Which merely means somebody reported it, and they have no idea what to
do with the report except pass it on.
PI = package insert. People have to realize that a package insert for a
drug is not a scientific document. It is an screed writen by drug
company lawyers and vetted by the FDA, all with the explicit purpose of
trying to minimize the responsiblity of either, by reporting everything
from legitimate statistics to a few pure anecdotal reports which could
be nothing more than the result of a mistake, an allergy, some other
medical problem, or a panic attack. If the % isn't given, and there's
no control % either, you can pretty well ignore it.
I personally think somebody should do a study of the various horrors
caused by the pharamacy companies during their studies. Here's from the
package insert of a drug sold to the public right now (I'm rounding
figures): 6% drowsiness, 8% headache, 3% dizziness, 5% nervousness, 1%
light-headedness, 1% coordination and walking problems, 4% nausea and
vomiting.
Holy tamales! And that's the PLACEBO group. (The study was on
triazolam/Halcion, a sleeping pill famous for causing amnesia, which by
the way didn't show up because they didn't ask about it). Look at the
damage done to people's quality of life by placebos. It's right there
in black and white (and please don't suggest that we need a placebo
control for the negative placebo effects, because you know that will
only cause more problems).
Here's the placebo group for Vioxx: 4% abdominal pain, 1% fatigue, 2%
dizziness, 3% flu-like syndrome, 1% leg edema, 8% respiratory
infection, 1% hypertension, 7% diarrhea, 3% dyspepsia, 3% epigastric
discomfort, 4% heartburn, 3% nausea, 2% sinusitis, 2% back pain, 8%
headache, 1% bronchitis, and 3% urinary tract infection. Ouch. Put
these lists together and it looks like a group of people poisoned with
something really nasty.
Now, notice that the % for dizziness and headache was very much the
same for both placebo groups. But the placebo for Halcion causes 6%
drowsiness, whereas the one for Vioxx apparently doesn't cause people
to be sleepy at all. Strange. And the placebo for Vioxx was just hell
on the stomach. Boy, it's a good thing the Vioxx guys didn't send their
placebo pills to the Halcion people and vice versa, or it would have
been really confusing. All those people supposed to be having stomach
problems and they're falling asleep instead :).
Now, it could just be that the harder you look for toxic effects in
your pills (sugar pills or not) the more of them you'll find. But if I
said that, I'd be acused of shilling for the pharm companies. So I
won't. I'll just suggest that these companies look for less toxic
placebo pills in their studies. Whatever it is they are using, it looks
like it may be causing up to 7% of people to have symptoms so severe I
don't know how they can work at any job which requires concentration
and doesn't let you work while sitting on the toilet. Some no doubt
have already lost their jobs, and are suing for disability.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med,sci.med.pharmacy
Subject: Re: statins don't reduce dementia risk
Date: 23 Jul 2005 15:06:24 -0700
Message-ID: <1122156384.612460.48550@f14g2000cwb.googlegroups.com>
Sharon Hope wrote:
> How many in the placebo groups you quote had amnesia?
COMMENT:
Not enough to generate a number, so less than 1%.
But not enough to generate a number in the Lipitor trials, either.
Unfortunately, there's some asymmetry in placebo vs drug reporting. In
package inserts, any effect in the placebo group that occurs with
frequency less than 1%, they are allowed to list as "-". But
contrarily, if there are ANY reports of negative problems in the active
drug arm at all, no matter the %, they have to list them as "possible
adverse events." If they were fair, they'd treat these both exactly
the same. But they don't. This is the FDA and the legal system's way of
looking for "truth." LOL.
We are talking about VERY RARE EVENTS, here. Despite a few docs like
Golomb shooting her mouth off to ABC news (without benefit of
statistics or studies to back her up), cognitive problems with statins
are so rare that no placebo-controlled study has yet been able to
demonstrate them. Despite looking carefully for them, as in the recent
Alzheimer's prevention study.
So if they're out there, they are RARE. To rare to quantify. Okay?
Maybe so rare they don't really exist.
The problem is that sometimes ordinary people really DO lose their
cognitive abilities (and their other abilities) for reasons which
aren't really easily fitted into some neat diagnostic category of
diseases we recognize diagnostically in 2005. Babies get "autism". Men
come back from wars like Vietnam or the Gulf Wars all screwed up
mentally and physically, but with no obvious trauma. And yet unable to
function. And people come down with chronic fatigue and can't get out
of bed, let alone work at a job. These are all medical mysteries.
Alas! There is no mystery which somebody doesn't have an answer for.
Following all these poor people who have a real physical disease (in no
doubt many cases) but no formal diagnosis, are a gaggle of
witchhunters, looking for something or somebody to blame. The chelators
and voodoo environmentalists. Most of them toxin witchhunters, but a
few infectious disease witchhunters, too. But they all live in a toxic
world, and by god, if you've got a funny medical problem they'll FIND
you a toxin to explain it. It's mercury in your vaccine, or if not
there, the mercury in your teeth. If it's a drug you took, well then,
it's that. If you were in Vietnam, it was agent orange. If you live in
East Bean Gas, it's something in your air or even your ground water. Or
it's mold in your walls. If you went to the first Gulf War, it was some
shot the military gave you. And if you went to the second Gulf War, it
was some OTHER shot they gave you for THAT one. And so on.
I'm afraid Dr. Beatrice Golomb, Darling of the Statin-Nightstalkers, is
one of these people. When not looking for toxic effects from statins
she's advising the military that some fraction of "Gulf War Syndrome"
in this last war (need I fill you in on the symptoms-- they'll sound
very familiar) is due to pyridostigmine shots. THERE'S yer toxin. Are
you happy? Sorry they weren't taking Lipitor, but you can't have
everything.
Now the problem with all of this, is that when she wasn't solving Gulf
War Syndrome, Dr. Golomb has had it in for statins for years. At first
she thought they weren't cost-effective (and she may be right, let's
admit it). Then she managed to collect a lot of money from the NIH to
do a placebo controlled study to look for their adverse effects. I have
to admire her salesmanship. Then she's been talking to the press about
the results she expects to find, even though she should not have broken
any codes, and probably hasn't even collected enough subjects. And
she's been writing articles emphasizing negative-effects or lack of
positive effects in subgroups in OTHER people's statin studies.
A whisper of inspiration suggests to me that she'll eventually find
what she's been primed to find, in her own study. But meanwhile, no
other studies have been backing her up. And in science, your buzz with
ABC news only lasts you so long.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med,sci.med.pharmacy
Subject: Re: Lipitor users have 38,461% more Amnesia than the normal population
Re: statins don't reduce dementia risk
Date: 23 Jul 2005 14:16:30 -0700
Message-ID: <1122153390.491668.299240@o13g2000cwo.googlegroups.com>
Sharon Hope wrote:
> 2% on Lipitor experience Amnesia
COMMENT:
No. Wrong. That is NOT what the PDR/PI says. The report of amnesia
(along with dozens of other possible adverse symptoms) occured at a
rate of less than 2%, and they report it that way, because possible
adverse events that are reported to occur at rates of 2% OR MORE in
clinical trials of a drug, are singled out for special mention (and are
printed at the beginning of lists in italics). Amnesia isn't one of
these. It's one of the rest of the possible adverse reactions which, no
matter how rare, are grab-bagged as "< 2%". We don't KNOW how much
less than 2%. For all we know, it might be 0.005%. There's no point in
guessing. It only takes ONE report from ONE doctor on ONE patient in a
clinical trial of of a modern drug to include this possible ADVERSE
event on a package insert. It's an observation which is essentially
anecdotal, and no statistics can be done for it. AGAIN, ONE REPORT OF
ONE PATIENT GENERATED BY ONE DOCTOR IN ANY CLINICAL TRIAL REPORTED TO
THE FDA FOR A DRUG CAN RESULT IN THIS. So for Lipitor, we know exactly
this much: At least some patient somewhere in some clinical trial of
Lipitor thought they had amnesia during the trial, or else their
physician did. That is all.
> 0.0052% of the normal population experiences Amnesia (5.2 per 100,000
> people)
> So, that equates to:
>
> People on LIPITOR have THREE HUNDRED EIGHTY FOUR TIMES THE RATE OF AMNESIA
> OVER THE GENERAL POPULATION.
>
> Lipitor users have 384.6 TIMES the normal frequency of Amnesia!!!!!!!!!!!!!
COMMENT:
No, it equate to nothing of the sort, for reasons explained.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med,sci.med.pharmacy
Subject: Re: Lipitor users have 38,461% more Amnesia than the normal population
Re: statins don't reduce dementia risk
Date: 23 Jul 2005 19:52:24 -0700
Message-ID: <1122173544.162944.92810@g49g2000cwa.googlegroups.com>
Dr. Wayne Simon wrote:
> of interest there are studies suggesting that lipitor decreases the
> incidence of dementia. and studies which suggest the opposite.
COMMENT:
Feel free to cite studies which "suggest the opposite." I can find
none. There is one investigator claiming to find small negative
cognitive effects from 2 statins on some parts of a psycholgical test
battery. But these are so small they can be identified only by
reference to the control group, and are not large enough that any would
show up alone, or be in danger of being diagnosed as "dementia."
Indeed, the difference is between performance enhancement on some tests
due to practice, and no enhancement (but no decrement, either).
These minimal findings have yet to be confirmed by any other
investigators. They are interesting, but of little relevence in any
discussion of dementia (or any type of severe and permanent cognative
deficit).
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: statins don't reduce dementia risk
Date: 23 Jul 2005 17:03:57 -0700
Message-ID: <1122163437.059527.305810@g14g2000cwa.googlegroups.com>
Sharon Hope wrote:
>
> As we now know from Dr. Golomb's research, Cognitive Damage is second only
> to muscle damage (myopathy, myositis, muscle pain, mitochondrial damage) in
> the incidence of adverse effects from statin drugs, including Atorvastatin
> (aka Lipitor), fluvastatin (aka Lescol), lovastatin (aka Mevacor),
> pravastatin (aka Pravachol), simvastatin (aka Zocor), rosuvastatin (aka
> Crestor), and cerivastatin (Baycol),
COMMENT:
Who is this "we"? Sorry, but "we" know no such thing from "Dr. Golomb's
research." Unless she publishes it only at your house, and fails to
let the medical community know of it?
> We know that M. Muldoon has shown that statins cause measurable cognitive
> damage in people after only 6 months on the drug, repeatably with different
> statins and different dosages of statins.
COMMENT:
We "know" no such thing. One researcher's finding of a failure to
improve on some few aspects of a very sensitive battery of
neuropsychiatric tests (as compared to controls, who did improve a
little with practice), cannot be labeled as "damage." At least not
until it is known whether or not it is reversible once the drug is
discontinued, and how rapidly.
And it certainly isn't "dementia," which is a clinical diagnosis which
is reasonably well-defined, according to DSM criteria. People who score
in the normal range on a neuropsychological test, and then fail to
improve their scores 6 months later, are not "demented." Nor would
anybody reasonably even imagine that they were headed in that
direction. It's a *very* mild adverse cognitive effect of statin drug
seen in people still taking the drug, and (in this case) an effect seen
with two statin drugs which are known to enter the brain. "Damage",
"dementia," and "Lipitor" are not appropriate words to use in this
context.
> What did they do to identify and differentiate the statin-caused dementia in
> the group of people who took the statin for up to 5 years in this study?
There **is no evidence** of any statin-caused dementia in this study. I
know that's hard for you to take, because it conflicts with your world
view. But there it is.
> They found " there were 480 cases of dementia, including 245 attributable to
> Alzheimer's disease alone."
>
> HOW MANY OF THE 235 CASES OF NON-ALZ DEMENTIA WERE DIRECTLY ATTRIBUTABLE TO
> THE SECOND MOST COMMON ADVERSE EFFECT -- STATIN-CAUSED MEMORY LOSS AND
> COGNITIVE DAMAGE?
COMMENT:
Why, none of them. Since the risk of dementia after 5 years was not
statistically different between users of statins and those who had
never used them. A study which finds no protective effect of statins on
risk of developing dementia, would just as surely find an
ANTI-protective (dementia causing) effect of statins, if there was one.
Or at least, if there was a big one. Very small effects either way can
always hide in underpowered studies. That goes without saying.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,sci.med.cardiology,sci.med.pharmacy,misc.health.diabetes
Subject: Re: study: statins may induce neuronal apoptosis
Date: 23 Jul 2005 15:40:10 -0700
Message-ID: <1122158410.430845.282760@g43g2000cwa.googlegroups.com>
mmlevy46@hotmail.com wrote:
> as per "petri dish" experimentation. one must begin someplace--where
> do you think most scientific studies begin if not in a laboratory
> setting.
COMMENT:
This is medicine, and the answer to that question is a little too
involved for me to want to get into. But suffice to say, it doesn't
have a simple answer.
> extrapolation to humans is a leap, though used for hypotheses
> all the time.
COMMENT:
Using the appropriate model, yes. Choosing that model, however, is an
art.
If there really were a good animal model for statin dementia with a
brain entering drug like simvastatin, that would be one thing. The
direct effect on neurons would be the natural next place to look.
And even if there were an animal model for statin dementia with
Lipitor, there would be little point to be gained by pulling out
neurons, putting them in a dish, and dumping atorvastatin directly on
THEM. That would be just.... stupid. Since that kind of thing can never
happen in the intact animal, what are you trying to find out?
In fairness to the researchers, however, they're not that stupid. They
are talking about statins which get into the brain, and the people
trying to use their research to support their clinical theories, are
talking about Lipitor. Apples and Oranges.
> and i would advise you to wait until absolute
> scientific proof of any detrimental effects to determine your statin-
> taking status. the statins under discussion are able to cross the
> blood brain barrier.
COMMENT:
The statin under discussion by the statin stalkers, and the one held up
to the most popular alarm as THIEF OF MEMORY, is atorvastatin/Lipitor.
And your evidence that it crosses the blood brain barrier in
significant amounts is, what?
Notice, please, that I'm not saying that there's no way Lipitor could
cause cognitive effects if it doesn't get into the brain. What I am
saying is that it if doesn't get into the brain, there's little point
in doing experiments with it in dishes of naked neurons. AGAIN,
whatever Lipitor does to intact brains (if anything) will be indirect,
and is NOT what what it's going to be doing, when dumped onto neurons
exposed in a dish. Why are you having difficulty with this concept?
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,sci.med.cardiology
Subject: Statins and Dementia
Date: 23 Jul 2005 17:36:39 -0700
Message-ID: <1122165399.212614.86110@o13g2000cwo.googlegroups.com>
Here is the abstract of the paper generating the noise:
1: Arch Neurol. 2005 Jul;62(7):1047-51.
Statin use and the risk of incident dementia: the Cardiovascular Health
Study.
Rea TD, Breitner JC, Psaty BM, Fitzpatrick AL, Lopez OL, Newman AB,
Hazzard WR, Zandi PP, Burke GL, Lyketsos CG, Bernick C, Kuller LH.
Department of Medicine, University of Washington, Seattle 98101, USA.
rea123@u.washington.edu
BACKGROUND: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase
inhibitors) reduce cardiovascular risk through mechanisms that might
affect the development of dementia. OBJECTIVE: To evaluate whether statin
use is associated with a lower risk of dementia compared with never use
of lipid-lowering agents (LLAs). DESIGN: Cohort study of
community-dwelling adults 65 years and older. The analysis included 2798
participants free of dementia at baseline. MAIN OUTCOME MEASURES: Using
Cox proportional hazards regression analysis, we estimated the risk of
incident all-cause and type-specific dementia associated with
time-dependent statin therapy compared with never use of LLAs. The
primary analyses incorporated a 1-year lag between exposure and outcome.
Secondary analyses included the final year of exposure and modeled statin
use as current use vs nonuse to simulate a case-control approach.
RESULTS: Compared with never use of LLAs, ever use of statins was not
associated with the risk of all-cause dementia (multivariable-adjusted
hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.77-1.52),
Alzheimer disease alone (HR, 1.21; 95% CI, 0.76-1.91), mixed Alzheimer
disease and vascular dementia (HR, 0.87; 95% CI, 0.44-1.72), or vascular
dementia alone (HR, 1.36; 95% CI, 0.61-3.06). In contrast, in secondary
analyses, current use of statins compared with nonuse of LLAs was
associated with HRs of 0.69 (95% CI, 0.46-1.02) for all-cause dementia
and 0.56 (95% CI, 0.35-0.92) for any Alzheimer disease. CONCLUSIONS: In
this cohort study, statin therapy was not associated with a decreased
risk of dementia. Methodological differences may explain why results of
this cohort investigation differ from those of prior case-control
studies. Additional investigation is needed to determine whether and for
whom statin use may affect dementia risk.
PMID: 16009757 [PubMed - in process]
COMMENT:
So the confidence limits for development of all-cause dementia in
people who had used statins vs. never used them, was 1.08 [.77 - 1.52].
Since this included a 1-year lag, it's less likely to be biased by
people being taken off statins due to developing dementia (not likely
in today's medical climate, but in theory possible), or (more likely)
being put ON statins due to developing some kind of dementia
(especially a multi-stroke caused type). Basically, however, no
difference was seen. The dementia subtype numbers are wider, and none
of them reach significance either.
In a secondary analysis which divided people by CURRENT use of statins
compared with non-use (which would be more sensitive to an immediate
current dementing effect of the drug), the hazard ratio for all
dementias was .69 (.46-1.02). This is very close to finding a positive
result for statins (i.e., non-demented people found significantly more
likely to be taking a statin). This is an odd result. It may reflect
some withdrawal of statins from people who develop dementia, but one
suspects that it's hardly likely to be because anyone suspects the
statin of being contributory. More likely is that doctors and families
quit trying to hard to prevent heart attacks in people who become
demented (and who are often institutionalized). In any case, there is
no way of interpreting any of these numbers to suggest that statins
cause very much dementia.
Here's a review reminding us that the positive epidemiological studies
on statins which seem to show a protective effect on dementia, are
flawed in various ways. And indeed they are. Prospective randomized
trials have shown no effect of statins on dementia progression ---
either positive OR negative. We lack good prospective evidence that
statins delay or prevent dementia of any time. But if statins CAUSED
dementia, one would expect all the numbers to go the other way. nd we
certainly would have seen a negative result in the randomized
intervention trials.
J Fam Pract. 2005 Jul;54(7):626-7.
Do statins delay onset or slow progression of Alzheimer's dementia?
Suchecki SA, Aitken PV Jr, Potts R, Collins LJ, Modi S.
University of North Carolina, Chapel Hill; New Hanover Regional Medical
Center, Wilmington, NC USA. E-mail: slade.suchecki@nhhn.org.
Statins (coenzyme-A reductase inhibitors) should not be used with the
single intent to delay the onset or slow the progression of dementia. Large
randomized control trials (RCTs) found that the administration of a
statin had no significant effect on preventing or slowing all-cause
cognitive decline (strength of recommendation [SOR]: A, based on large
RCTs with narrow confidence interval). Specifically, there is
insufficient evidence that statins delay the onset or slow the
progression of Alzheimer's dementia (SOR: B, based on systematic review
with heterogeneity). While 3 epidemiologic studies have found a
decreased incidence of dementia among those taking statins, these
studies have significant methodological shortcomings and do not show a
causal relationship (SOR: C, based on poor-quality studies).
PMID: 16009093 [PubMed - in process]
Next is the first 12 months of a small but randomized prospective trial
of Lipitor for dementia. It is weakly positive-- not very impressive.
But if Lipitor (here used in high dose at 80 mg a day) was the brain
toxin it's been painted as, we surely would NOT see the results below
Arch Neurol. 2005 May;62(5):753-7.
Atorvastatin for the treatment of mild to moderate Alzheimer disease:
preliminary results.
Sparks DL, Sabbagh MN, Connor DJ, Lopez J, Launer LJ, Browne P, Wasser D,
Johnson-Traver S, Lochhead J, Ziolwolski C.
Author Affiliations: Sun Health Research Institute, Sun City, AZ 85351,
USA. larry.sparks@sunhealth.org
BACKGROUND: Laboratory evidence of cholesterol-induced production of
amyloid beta as a putative neurotoxin precipitating Alzheimer disease, along
with epidemiological evidence, suggests that cholesterol-lowering statin
drugs may favorably influence the progression of the disorder.
OBJECTIVE: To determine if treatment with atorvastatin calcium affects
the cognitive and/or behavioral decline in patients with mild to
moderate Alzheimer disease. DESIGN: Pilot intention-to-treat,
proof-of-concept, double-blind, placebo-controlled, randomized (1:1)
trial with a 1-year exposure to once-daily atorvastatin calcium (80 mg;
two 40-mg tablets) or placebo using last observation carried forward
analysis of covariance as the primary method of statistical assessment.
PARTICIPANTS: Individuals with mild to moderate Alzheimer disease
(Mini-Mental State Examination score of 12-28) were recruited. Of the
98 participants providing informed consent, 71 were eligible for
randomization, 67 were randomized, and 63 subjects completed the
3-month visit and were considered evaluable. MAIN OUTCOME MEASURES: The
primary outcome measures were change in Alzheimer's Disease Assessment
Scale-cognitive subscale and the Clinical Global Impression of Change
Scale scores. The secondary outcome measures included scores on the
Mini-Mental State Examination, Geriatric Depression Scale, the
Neuropsychiatric Inventory Scale, and the Alzheimer's Disease
Cooperative Study-Activities of Daily Living Inventory. The tertiary
outcome measures included total cholesterol, low-density lipoprotein
cholesterol, and very low-density lipoprotein cholesterol levels.
RESULTS: Atorvastatin reduced circulating cholesterol levels and
produced a positive signal on each of the clinical outcome measures
compared with placebo. This beneficial effect reached significance for
the Geriatric Depression Scale and the Alzheimer's Disease Assessment
Scale-cognitive subscale at 6 months and was significant at the level
of a trend for the Alzheimer's Disease Assessment Scale-cognitive
subscale, Clinical Global Impression of Change Scale, and
Neuropsychiatric Inventory Scale at 12 months assessed by analysis of
covariance with last observation carried forward. CONCLUSION:
Atorvastatin treatment may be of some clinical benefit and could be
established as an effective therapy for Alzheimer disease if the
current findings are substantiated by a much larger multicenter trial.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 15883262 [PubMed - indexed for MEDLINE]
================
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,sci.med.cardiology
Subject: Re: Statins and Dementia
Date: 25 Jul 2005 16:18:29 -0700
Message-ID: <1122333509.218856.184870@o13g2000cwo.googlegroups.com>
Sharon Hope wrote:
> > COMMENT: get the point?
>
> Yes, the point is you are intentionally obfuscating a point that you are
> uncomfortable with - Statin drugs cause AMNESIA at a staggeringly
> disproportional rate.
COMMENT:
No, there's no way to tell what the rate is, because there are no
reports of amnesia rates and placebo rates from controlled studies.
Thus ratios cannot be calculated. "Disproportional" is a word that
cannot be used. If the rate is 7 in 2502 people (the Lipitor approval
trial), then that's 0.28% (not 2%), and we still need to know then what
was the rate in the placebo group in that trial? We don't.
> The authors of the books you list in your pathetic attempt at misdirection
> do not have the letters "M.D." following their names.
COMMENT:
Hey, if crazy books by M.D.'s turn you on, read any book by Lorraine
Day, M.D. If you thought M.D.s were infallible we wouldn't be having
this conversation, would we?
> The books you site do
> NOT address statin-induced AMNESIA.
COMMENT:
So? There are a lot of causes of amnesia. It's one of the 7 screening
signs of somatization disorder (know what that is?). It's a reported
side effect of both smallpox and anthrax vaccines (somehow, only
vaccines used in Gulf War Vets cause global amnesia).
> The three books that address statin-induced AMNESIA are all by physicians,
> and they have earned the "M.D." following their names.
COMMENT: There are 2 books by the same guy here (the former astronaut
Graveline). And they can "address" the problem all these like-- there
is still no good scientific evidence.
> >> "This study provides partial support for minor decrements in cognitive
> >> functioning with
> >> statins. Whether such effects have any long-term sequelae or occur with
> >> other cholesterol-lowering interventions is not known." This is the
> >> second of two
> >> studies by Muldoon, both showing measurable cognitive decline in statin
> >> groups after
> >> only 6 months, using Neuropsych testing. Further, the cognitive deficits
> >> appear
> >> consistently in specific areas.
> >
> >
> > COMMENT
> > Wrong! You are absolutely misquoting the papers, which say no such
> > thing (full abstracts appended). There is no measurable decline in
> > scores in any statin group. What happens is that the scores don't
> > improve as much as the placebo groups.
> >
>
> Wrong. Some scores declined, in others there was a failure to thrive. The
> statin users simply could not continue to learn at a normal rate. THAT IS
> A SERIOUS PROBLEM.
COMMENT:
It is not a serious problem. The amount here was a "minor decrement",
as the author
of the study said. So minor it had to identified statistically. You
might get something far
worse from taking an antihistamine.
> No parent I know is happy when their child leaves high school reading at the
> 3rd grade level, despite your observation that he began school reading below
> the 1st grade level.
COMMENT: That wouldn't be a minor decrement, now would it? If would
show up on testing even *without* a control group, wouldn't it? A 2
year developmental delay would stand out like a red light, wouldn't it?
> In some scores, the statin users learned NOTHING in the 6 months while on
> statins.
COMMENT:
No. The fact that they didn't improve their scores on some aspects of
the same test 6 months later hardly means they "learned nothing." If
just means they didn't improve their scores in a few areas. If any of
them had had global amnesia of the kind which has been blamed on
Lipitor, they couldn't that taken these tests at all, because they
wouldn't have been able to remember their own names, let alone the
detailed personal information necessary to participate in a clinical
trial and take a neuropsych performance test. Get real.
> If you were an employer and you hired two equally qualified people for a
> particular job. After 6 months, one had learned how to do the job specific
> to your company and the other, the person who was taking statins, had
> learned no more about the job than he knew the day he was hired.
>
> Which one would you keep?
COMMENT:
This was not 6 months of training. It was two tests taken 6 months
apart. The only "training" was having taken the test before, 6 months
ago. It's not clinically significant. Furthermore, it wasn't a global
problem, but showed up only on performance areas related to attention.
It could equally well have been due to statin users being more relaxed,
and the self assessment well-being profiles of these very people, in
the same study, actually suggested *exactly that.* So?
> THAT IS A SERIOUS PROBLEM.
>
> > Furthermore, the differentials are so small that the researchers needed
> > neuropsych tests and a control group to find them (nobody claimed that
> > interfered with functional activities to any noticeable extent, and
> > Muldoon makes that very point). Nor have they been repeated and
> > confirmed by any other groups.
> >
>
> THAT IS ABSOLUTELY NOT TRUE.
>
> This study was done 3 times, each time placebo controlled, and IN ALL THREE
> STUDIES THE STATIN GROUP EITHER LOST COGNITIVE ABILITY OR FAILED TO LEARN AT
> A NORMAL RATE.
COMMENT:
It was done 3 times by the SAME group of researchers. It's a small
effect. It has not been *independently* confirmed (that means by other
scientists-- science is not "confirmed" by the same guys getting the
same results each time).
> EACH OF THE THREE STUDIES FOUND MEASURABLE COGNITIVE DECLINE IN THE STATIN
> GROUPS AFTER ONLY SIX MONTHS OF TREATMENT.
COMMENT:
No, there was no cognitive decline. Cognitive declines are measured by
test performance declines. And to be robust, they had better be BIG
declines. Otherwise you don't know if they're not just due to the guy
taking a drug that relaxes him.
> STATINS ARE MARKETED AS A LIFE-LONG TREATMENT.
>
> What kind of continued decline can we expect when the treatement extends
> BEYOND SIX MONTHS?
COMMENT:
None! And you shouldn't either, especially given the fact that I think
it was you who suggested that lack of cognitive decline in the 3 year
PROSPER study could have been explained by a 6 week run-in, in which
everybody who was going to have severe statin effects washed out in
just 6 weeks, then the rest had no problem after that. I would say the
chance of having a terribly mild effect at 6 months and then have it
keep going into full dementia at 3 years, is pretty unlikely, in that
case, wouldn't you?
> My husband is one example. 4 years of Lipitor 10mg/day
> left this mid-50's corporate CEO (twice) with MULTIPLE WITNESSED EPISODES OF
> TRANSIENT GLOBAL AMNESIA AND SHORT-TERM MEMORY MEASURED AT BELOW THE 1
> PERCENTILE.
COMMENT:
Your husband is an anomaly, and if I read the net correctly, is
apparently becoming one of the sacred Stations of the Cross for
reporters and believers to visit, in their Calvary Statin Via Dolorosa
Pilgramage. Along with Golomb. So?
I'm not arguing it's impossible. Just very unlikely. Out of million of
people taking these drug, you can still do no better than to find me a
couple of trials of people who weren't paying attention enough to
better their previous scores, and some uncontrolled reports of 60 odd
case reports, many of which resolved, and at least one of them got
better enough afterword to write a book about it. Sorry, but I'm not
impressed. On the other side of it, are several large controlled trials
which found NO adverse statin effect on cognition, even though it was
looked for. PROSPER is one of them, and we've just discussed another
(the neuro arm of the CHS study, analyzed by Rea). The large signal IS
SIMPLY NOT THERE.
If you're married to one of the few guys whose life was destroyed by
statins, then you have my sympathy, but there are thousands of people
whose lives have been destroyed by aspirin. And not a few by accidents
with barbecue grills. And stepladders. And combinations of too much
beer and trying to do nearly anything complicated around the house.
These are horrible, but they don't really justify giant public
campaigns. Life is risky. A lot of very tiny risks that exist in life
means that over hundreds of millions of people, you're going to have
hundreds or even thousands who die every year in ridiculous and
freakish ways, like having a car come though your house wall, or being
struck by lightening in circumstances which really didn't warrent
special attention.
I'm sorry your husband was struck by lightening in some kind of way.
But, frankly, I'm tired of reading about him and this astronaut guy all
over the net. If this statin-induced brain destruction is a true global
pandemic, you ought to be able to recruit a lot most poster-children.
Sort of like MADD did (and does).
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,sci.med.cardiology,sci.med.pharmacy,misc.health.diabetes
Subject: Re: study: statins may induce neuronal apoptosis
Date: 25 Jul 2005 18:00:49 -0700
Message-ID: <1122339649.934851.70530@g47g2000cwa.googlegroups.com>
Sharon Hope wrote:
> > If there really were a good animal model for statin dementia with a
> > brain entering drug like simvastatin, that would be one thing. The
> > direct effect on neurons would be the natural next place to look.
> >
>
> IF? IF??? Dogs were eliminated from testing of statins early on because
> they suffered DRASTIC MEMORY LOSS and other BRAIN EFFECTS. They would bring
> a dog into the room, administer the statin, and the dog would be unable to
> find the door he just came through to exit the room.
COMMENT:
Really? They let the dogs find their way into, and out of, the
drug-administration rooms on their own, did they? Perhaps just them
parking validation?*
Really, I want you to quote exactly your source for this tall tale. It
must be one of those popular books, and anecdotal and several times
removed.
*[Beagles! Possibly the world's stupidest dog. I'm not even sure how
one would go about testing the critter's memory in the first place.
Excluding that for smells, the beagles I've known have shown no
evidence for a memory. And very little for a brain. A beagle is just a
nose attached to some legs; the package being far dumber than the
average lab rat].
> Dogs also suffered a
> high rate of HEMORRHAGIC STROKE on statins.
COMMENT:
Indeed. And on a hell of a high dose, also. Every drug has some toxic
effect somewhere. **But your husband didn't have a hemorrhagic stroke,
did he?** So you're not exactly helping your case here.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Statins may Protect Against Pneumonia Fatalities
Date: 29 Jul 2005 18:41:24 -0700
Message-ID: <1122687684.330134.102480@g47g2000cwa.googlegroups.com>
jay1000 wrote:
> Patients taking the cholesterol-lowering drugs known as statins were less
> likely to die from pneumonia, according to a recent study conducted by
> researchers from the University of Texas Health Center at San Antonio.
>
> Researchers measured the risk of dying from pneumonia in patients admitted
> to the hospital for it. They compared this risk among patients taking
> statins to those not taking statins. Study authors used the Pneumonia
> Severity Index to rate death risk within 30 days of hospital admission.
> Results show those taking statins were nearly three-times less likely to die
> than patients not on statins.
>
> SOURCE: Respiratory Research, 2005;6,82
COMMENT:
Was this controlled for lipid levels? Because if it wasn't, there's a
problem. The usual caveats about post-hoc associational epidemiology
apply. Association is not causation. This does NOT necessarily mean
that statins protect against pneumonia death. It may very well be that
(instead) high LDL levels do, and taking statins is simply a marker for
people with lipid problems.
LDL does have functions in the body other than to give people heart
disease :). Among other things, there's some evidence that bacterial
endotoxins are absorbed and inactivated by LDL.
In the gigantic China Study, the largest study of blood predictors of
disease and actual disease and death statistics ever done, there's an
impressive correlation between very low LDL levels and risk of death
from pneumonia. You don't get any extra protection from heart disease
with TOTAL cholesterol going from 125 (which was the mean for rural
Chinese) to 90 (which was at the lower end of their spectrum. But your
risk of dying of pneumonia does go up a lot.
In any case, statin users probably still have higher LDL levels than
the general population. We may have found a place where that actually
does them some good.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Statins may Protect Against Pneumonia Fatalities
Date: 30 Jul 2005 10:01:05 -0700
Message-ID: <1122739497.812686.323060@z14g2000cwz.googlegroups.com>
Sharon Hope wrote:
> It would be interesting to see how this study was 'spun' given the well
> established adverse effect of statins: suppression of the immune system.
COMMENT:
All in all, it's hard to know. You want a working immune system, but
you don't want it to work too hard, since in the process of cleaning
out bacteria and viruses, a normal immune system sometimes destroys a
lot of good tissue, like in the bad old days with cops wiping out city
blocks battling radicals like MOVE or the Simbionese Liberation Army.
"We had to destroy the village in order to save it" wasn't just
invented in Vietnam; sometimes your body thinks that way, not knowing
about antibiotics or antivirals.
Immune suppression is the other candidate for the proximate effect on
pneumonia in this study, as it's quite possible for people to die of
septic shock during an infection, and in that case, suppression of an
over-reacting immune system is what you may want to do. Again, in some
cases the immune response to infection is worse than the infection.
Children with infectious meningitits are given steroids for this
reason. One day, to some people we may give statins.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Lipitor users experience Amnesia 38,461% more frequently than the
normal population
Date: 31 Jul 2005 20:24:44 -0700
Message-ID: <1122866684.731475.60650@g49g2000cwa.googlegroups.com>
Paul E. Lehmann wrote:
> Bill wrote:
>
> > Sharon, you keep avoiding the issue. You calim the Lipitor PI says amnesia
> > occurs at the rate between 1 and 2%. Anyone can look at it and see that it
> > does not. It says less than 2%. So this could possibily mean anything less
> > than 2% - perhaps just one person in the study.
> >
> >
> > Is this true or not true.
>
> 1.99% is less than 2% also. Obviously it is greater than 1% and it is not
> known how much rounding down to the nearest whole number was done.
COMMENT:
It is NOT "obviously" greater than 1%. There is nothing to show that it
wasn't exactly 0.028%, which I think is what the amnesia figure from
the 2502 patient study actually was, if the Pfizer rumored report of 7
amnesia patients is correct.
Lipitor PI's more recently for adverse reactions now refer ALSO to a
much larger and more recent ASCOT placebo-controlled study of about
10,305 patients. But it still doesn't report anything lower than 2% as
anything but "less than 2%". *Most* of these 100+ side effects
"obviously" occured in far less than 2%, because the total dropout rate
due to side effects in ASCOT was total only 2% (not significantly
different from placebo). Do the math. How many side effects can the
average person take? Do you really think 100 diffent side effects each
had percentages reported anywhere near 1%? Or maybe you think the 2%
who dropped out each had 50 different side effects, and the other 98%
were okay? LOL.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: 3/4 of people taking statins no benefit: none. zilch
Date: 1 Aug 2005 11:03:06 -0700
Message-ID: <1122919386.512835.271260@f14g2000cwb.googlegroups.com>
>> "Did the original article say that it helped 1/4 of the people. Yes or
>> no." It is a simple question.
>
>Also waiting. My guess is that Sharon is the thing she pretends to
>hate.
>No reply.
COMMENT:
Yep, she's a bigot. And it's pretty rare to find an honest bigot. Her
husband is ostensibly (but unprovably) the sufferer of what IS provably
a rare statin side effect, and she's nevertheless out crucading for
people getting a statin to be given some kind of test to make sure
nothing bad will happen to THEM. She figures her own rare personal
experience should make policy for everybody; people who will almost
certainly never see anything like she thinks she's seen. Narcissism on
stilts, is what this is.
You know, I wish there was a test we could give *everybody* to make
sure nothing bad would happen to them that day. On the street, on the
freeway, whatever. Alas, there isn't. We risk our lives to live as we
choose. All of us, everyday. Some of us lose at the gamble. We get
rear-ended and the gas tank burns and we end up covered with burn
scars, and now we have to find a witch. It's got to be the maker of the
Pinto or the Crown Victoria. This is pure Ralph Naderism of finding
somebody to blame for every single bad experience in life, excepting
maybe the weather. Witchhuntery. It's people who get a bad spin of the
roulette wheel or casino slots of life, and are complaining to the
casino manager that they've had bad really bad luck, unusually bad
luck, and now want their money back.
You can go through your entire life finding people who've had bad luck
in casinos, but such is human nature most of them are too embarrassed
to admit it. It takes a real egoist or paranoic to decide they've been
*specially* victimized in a casino.
Well, read the fine print at the bottom of your contract (or package
insert). Your milage may vary. Your stock MAY LOSE VALUE. You may have
a drug side effect, and if you're incredibly unlucky, it may be a very
bad one. This is planet Earth. You are an adult. There are no
guarantees here. Nobody gets out of it alive, and some people have a
very bad ride. I beg your pardon, we never promised you a rose garden.
GROW UP. If you lost money, you were not necessarily cheated. If your
gizmo breaks, you were not necessarily swindled. If you have a bad
medical experience, you were not necessarily the victim of incompetence
or sloth. And if your car crashes, it is almost surely NOT because it
was built to be "UNSAFE AT ANY SPEED." If you start thinking this way,
here is my message to you: you are nuts. You are hysterical, you are
paranoid, you are narcissistic, and you are still a child. We wish you
would get some treatment, unless you really are under 18 years old (in
which case we just wish you'd go someplace else until time fixes your
problem of self-centeredness.)
Thank you.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: 3/4 of people taking statins no benefit: none. zilch
Date: 1 Aug 2005 19:06:20 -0700
Message-ID: <1122948380.882296.124540@o13g2000cwo.googlegroups.com>
listener wrote:
> Wow. I just peeked my head in to see what was going on in the old
> newsgroup. Nice to see there are still some, like Steve, fighting the
> good fight but, really, sad to see the old conflagration is apparently
> still full speed ahead.
>
> The zee's and sharon's of the world have to hold on to their irrational
> agendas - without that....then what?
COMMENT:
Well, it's a helluvalot easier to backbite and kibitz the people trying
to fix a problem, than it is to tackle the problem directly yourself,
that's for sure. I've seen a lot of people criticising NASA who aren't
rocket scientists (and some who are-- but let's keep them separate).
I don't know what the Sharons and Zees would do without their drugs. I
guess they'd be out looking for toxins or polution or bad cars and
other bad tech, like the Naderites they inherently are. In this world,
there are engineers, and there are social engineers. Both are needed in
society, of course, but in my observation, only one of these groups
gets itself regularly confused with the other.
I've offered my opinion as to why that happens. In short, I think C.P.
Snow was right, and of the two cultures, typified by expertise in math
or language, only one has any real understanding of what the other does
for a living, and (strangely) it isn't the one that thinks itself truly
educated. But I can find you a lot more techies who can write a simple
declarative sentence than I can find you "cultural elite" who can
differentiate a simple function. In the modern world the elitism of the
litterati is wrong. There is just as much education and high culture in
knowing when to use a Torx screw driver, as there is in knowing who
knives who and why at the end of Henry VI part III. Maybe more.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: 3/4 of people taking statins no benefit: none. zilch
Date: 1 Aug 2005 15:49:38 -0700
Message-ID: <1122936578.570329.134820@z14g2000cwz.googlegroups.com>
Robert wrote:
> I am in awe of the respect you garnish from Zee and others.
COMMENT:
Huh?
> If I had said
> sharon was bigoted or anything like that I would and have been branded as
> insensitive, uncaring, drug pushing asshole.
COMMENT:
Not if were true. If Sharon's husband had died in a airliner crash and
her _cause célèbre_ was the supposed incompetence and unsafety of all
airliners (or even Pan Am -- pick your subset), it would be obvious to
you that she had some mental problem, and was an airline bigot. And
also why. Ditto if her mate had been killed on the space shuttle and
she was going on and on about how they didn't know what danger they
were in (rather like MacAuliffe's husband did--- but hey, it WAS the
*&%$ing SPACE SHUTTLE. If the thing wasn't dangerous there'd be no
point admiring the people who ride it).
Such people who cannot tolerate or understand risk do exist, and they
are obviously politically effective. They're responsible for you having
to take your shoes off at all airports. They grounded the shuttle for
years, and would have it grounded now if it weren't up there already
(and would keep it up there until it was proved safe and effective,
except there's the little problem of life expectancy if nobody does
anything, which is what these people really desire out of life-- to
keep anybody from doing anything interesting).
But the problem in life is that LIFE is not perfectly safe. And some
people aren't very safe, just sitting there breathing (like the folks
on the shuttle). If you happen to have heart disease and/or several
risk factors for it, from diabetes to male gender to hypertension to
high cholesterol, your life expectancy is shortened. In that case, it
may well be lengthened by taking one of the statins, and studies do
indicate this. However, as you subtract risk factors, the case for
taking any of these drugs becomes less and less clear, until finally
you get to a gray area where the answer to whether it is safer to take
the drug or not to take it, is simply unknown. At that point, we need
to stop and simply say that.
However, this issue has gotten polarized. Sharon is claiming mental
side effect rates for statins that they manifestly do not have, and
when confronted with this, merely says that her husband's side effect
rate was 100%. That's nutty thinking. We have people pointing out that
statins haven't been shown to save lives in primary prevention, even
though they must know the studies this judgement is based on, were
deliberately stopped at secondary endpoints before this primary
endpoint could be reached, so *by study design* it has been, and still
is, impossible to *show* that statins save lives in primary prevention,
even if they did. You can't handicap a drug and then claim it doesn't
work.
Even some medical publications are crazy. I am looking at British
Columbia U therapeutics letter (yes, medical moroons from Canada,
again-- maybe even some you know) which argues that even though there
is an absolute 1.8% reduction in stroke and MI in 2 primary prevention
trials, there is no reduction in the 44% "serious side effect rate," so
that something might be "making up for" the stroke and MI. Duh. Do I
have to point out to you that if these drugs had a 44% rate of any side
effect at all *comparable* to a stroke or heart attack, that they
wouldn't sell *at all,* let alone be a multibillion dollar industry?
No? Thus, apples and oranges are being compared, and health
professionals are doing it (albeit Canadian ones). And anybody standing
in their way is labeled as a pharmacy shill.
> Zee has many doctor friends she has dinner with and they just node their
> heads in a patronizing manner every time she gets on a tirade.
COMMENT:
So? I too have had dinners with crazy people without telling them how
crazy they were. Haven't we all? But this here (sci.med) is a
different venue, and lives are at stake. Here, I call them as I see
them, and you get no social credit for saying things that may well get
somebody dead before their time. I'm going to call you on it, and if
you disagree, you can get out your stats. But you'll probably lose. And
if you win, you'll get to see me change my mind in public, as I did
about many aspects of HRT. If you aren't a bigot, you are capable of
changing your mind when faced with the evidence. If you ARE a bigot
(bei Gott--person who thinks god is on their side and is intolerant of
any but their own unreasoning and prejudiced opinion), it doesn't
matter what evidence you're faced with.
COMMENT:
> I don't have a lot of doctor friends and don't want any.
Another bigot. Shrug. Your loss if you automatically dismiss any class
of people whatever.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: 3/4 of people taking statins no benefit: none. zilch
Date: 1 Aug 2005 17:17:46 -0700
Message-ID: <1122941866.427515.193070@g47g2000cwa.googlegroups.com>
just Ed wrote:
> You left out the rest of the conclusion of the UK study:
> "These findings, which are based on large numbers of deaths and
> non-fatal cancers, provide considerable reassurance that lowering total
> cholesterol concentrations by more than 1 mmol/L for an average of 5
> years does not produce adverse effects on non-vascular mortality or
> cancer incidence."
>
> IWO there was no benefit to be claimed in other than the high risk
> group. It didn't hurt them.
>
> your reference is in line with zee's post.
> You have made no point at all.
COMMENT:
Look, there IS evidence of prevention of strokes and MIs by statins in
several primary trials. It's small, but it's statistically there, and
in that sense, is real. About all you can really do about it is argue
that it's not worth the money, or is counteracted by side effects---
not that it doesn't exist.
Some have tried to argue that it exists but isn't important, that
mortality isn't influenced, so that maybe statins are killing people by
other mechanisms to make up for the lives saved in stroke and MI. I
don't think anybody really believes that, looking at the mortality data
from the very large secondary trials. If extra mortality from other
causes was there, we'd see it THERE. We don't, as you yourself
recognize. And we all know the primary trials were stopped early, so as
to make this kind of mortality finding impossible to generate, even if
it existed. I think that's sufficient for that argument.
You CAN play the game of arguing that that the strokes and MIs in
primary prevention aren't worth the MONEY and TIME and BOTHER. At least
that's HONEST. It's also a valid argument on an individual basis (how
much is YOUR time and money worth, vs a tiny risk-- only you can say),
but it's one that socialists perhaps cannot come to grips with. If
you're a socialist, your whole society has to come to some democratic
decision on how much money and bother a few months of your life is
worth. The idea that you might want to attempt such a judgement
*yourself* makes many Europeans and Canadians dizzy. Their mental
circuit breakers then blow, and they are required to make a virtue of
necessity, if there's some reason they have no access to statins, or
for some reason cannot take them.
Finally, if you can't admit that perhaps MIs and strokes CAN be
prevented in those majority of people who are taking them as a result
of primary risk factors only (albeit at high cost), then there's only
one place for you to run: the argument that side effects are so bad
with statins that they're just as sick taking them (on average) as if
they went ahead with their slightly larger risk of stroke and MI.
We've seen this argument here. I've criticised it. The reduction in
stroke and MI is on the order of 1 or 2%, and there's no evidence from
any statin study of side effects as bad as a stroke or MI, at anything
like that rate. Indeed, dropout rates are 2% typically in primary
studies, and that looks like placebo dropout rates, and isn't
significantly different from it. If we had *another* 1% or 2% of people
having problems as bad as stroke or MI from their statin, WHERE ARE
THEY? Dying of myopathy and dementia in institutions, but refusing to
stop their pills, we're told. And not getting their data into the study
side effect profile rates....
Say what? Having seen the dropout rate and compliance rate for blood
pressure pills and diabetes meds, for side effects far less distressing
than dementia and total asthenia, all I can say to such arguments, is
that I've got a bridge in Brooklyn to sell ya. In short, I'm tired of
the "I took statin pills still I looked like Stephen Hawking, but I
could not stop" story. Sharon tells it well, but we've heard it. It
doesn't work that way for any other primary preventive drug. For any
other class of preventive medication or therapy, people quit their
pills (or anything else they're doing in prevention) at the *least*
excuse, when they don't feel well. If I had a nickel for every diabetic
who told me they stopped their shots because they didn't feel good, I
could retire. Statins are not NSAIDS or HRTs, where actual and tangible
short-term benefits arguably might have blinded people to long-term
problems with health caused by them. But we're told that the statin
story is essentially the same one. Why? Why are we to think people are
welded to *this* particular class of preventive, unlike any other in
the history of medicine? I dunno.
I rather doubt that statins are physically addictive or
dependence-causing, and yet one cannot reconcile their continued very
wide use and reported very wide spectrum of side effects, otherwise. :)
Something certainly smells, there. You know where *I* think the truth
problem is.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,sci.med.cardiology,talk.politics.medicine
Subject: Re: selling sickness to the well
Date: 5 Aug 2005 19:07:25 -0700
Message-ID: <1123294045.307199.239310@g47g2000cwa.googlegroups.com>
Sharon Hope wrote:
> > Sharon Hope insisted on giving incorrect data about Lipitor
> > side effects in PIs and study results, and got her arugment handed back
> > to her in thin slices.
>
> Interesting, all my posts were supplied with source links and the math
> (correct and decimal error, favoring the other side) were carefully
> explained.
COMMENT:
Your "explanations" were faulty. It's not complicated. The incidence of
amnesia for Lipitor is not given exactly in any study. The information
is not formally available anywhere, and all we know about it, is that
it's an incidental reported at less than 2% rate, as are 100 other
miscellaneous side effects. No placebo-controlled study is available
which reports a greater incidence of amnesia in the Lipitor group than
in the placebo group. Thus, there is no good scientific evidence that
Lipitor causes amnesia at all.
I know of no controlled study in which cognitive decline has been
specifically tracked and evaluated for Lipitor. However, for Pravachol
(PROSPER) and simvastatin/Zocor (HPS) there was no difference between
cognative decline in treatment vs. placebo groups. These are sensitive
and large studies which found nothing significant in mental side
effects.
> Bottom line, regardless of all the uproar, is that amnesia occurs far more
> frequently among Lipitor users than among the general population.
COMMENT:
Bottom line is you don't KNOW what the incidence is in Lipitor users.
Nobody does.
Bottom line is even if you DID know what it was in Lipitor users, it
wouldn't mean a thing without a control group to compare it to, since
Lipitor users are preponderantly old sick men with vascular disease.
Their amnesia rates, whatever they are, can be expected to be different
than many other populations whose brain arteries are in better
condition.
Finally, even if you know the incidence AND you had a placebo group to
compare it to, you'd STILL have to apply a correction (such as the
Bonferroni) for multiple post hoc end points, unless you went into the
study a priori looking for amnesia *as an endpoint.* The REASON these
100+ side effects are reported as they are, is that it would be
meaningless to report 100 different p values, since by definition,
about 5 of them would be significant at p < 0.05, just by chance.
Fishing expeditions like the Lipitor marketting trials can't go around
reporting on the p value of 100 randomly reported effects. They CAN be
used to design for definitive trials like Golumbs, but hers won't use
Lipitor anyway. You'll still be stuck with Pravachol and Zocor results.
Ironically.
> But then, multiple published books and studies alread attest to this.
COMMENT:
3 popular books or so might "attest" to it. As for studies, I've yet to
find a well-controlled one that found anything different than placebo,
in any way that was reportable and correctable for the bias of multiple
post hoc tests.
> That
> you have some snide and disrespectful comment for each does not diminish
> these well-referenced published sources.
COMMENT:
No, what diminishes them is the quality of the studies themselves. The
better the design (prospective) and the larger and better randomized
and controlled a statin trial is, I think it's fair to say the less
it's likely to show any effects on mental decline, or indeed mental
effects at all. Either positive or negative. Unless you count the
effects from stroke, in which case (as in PROSPER) the results are
quite spectacular. But all in favor of the statin.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,talk.politics.medicine,sci.med.cardiology,soc.retirement
Subject: Re: stopping statins is bad for your health
Date: 7 Aug 2005 12:54:45 -0700
Message-ID: <1123444484.963304.41800@o13g2000cwo.googlegroups.com>
Poppy - San Francisco Bay Area wrote:
> I have been hearing about side effects from taking statins, in my
> stroke group. I would like accurate info about whether they are worth
> the risk.
COMMENT:
The HPS trial showed that people who already had evidence of
cerebrovascular disease (certainly a former stroke counts) had a 33%
reduction in risk of further stroke being complaiant with 40 mg a day
of simvastatin (Zocor). That's a big reduction--- the stuff prevents
one stroke in three in this group.
So yes, nearly everyone agrees that it's worth the risk, for stroke
patients. Despite all the propaganda you hear against statins here,
most statin side effects go away if you get them, and you stop the
pill. And in any case, they are rare (severe ones in total being
considerably more rare than 1 in 50 users, and probably more like 1 in
200 users if you subtract placebo rates).
A doctor named Golomb at UCSD has been collecting 1000 people to run a
statin side effect trial. That study was supposed to have been
concluded last year, and isn't yet. That tells me they managed to
collect the full 1000 people, and the trial wasn't stopped prematurely
by monitors for ethical reasons. That fact alone puts upper bounds on
how many severe side effects they could have seen. If the trial was
well-run and properly run, this number cannot have been large.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Question: blood test results
Date: 8 Aug 2005 20:57:23 -0700
Message-ID: <1123559843.271352.300490@g43g2000cwa.googlegroups.com>
Sharon Hope wrote:
> Education is positive, that is what I do.
COMMENT:
Education can be negative and biased. If you do that, you do harm.
> These adverse effects exist, and the numbers of people who are becoming
> disabled by them are growing alarmingly. It makes no difference how rare a
> condition might be if that condition affects you.
COMMENT
But before it affects you, and while you're making a drug decision, it
makes all the difference in the world how rare it is. Richard Feynman
once asked his surgeon what his chances were to survive a particular
operation, and the MD told him that you couldn't talk about the odds
of a single event. Feynman said "From one professor to another, you can
if it hasn't happened yet." Just so. Feynman was quite right.
> Futher, people who are considering taking statins or who are on statins
> deserve to know that Dr. Muldoon has published two gold-standard placebo
> controlled studies which show that for different brands of statins and for
> different dosages of statins there is, after only 6 months, a measurable
> cognitive degredation in those taking the statins.
COMMENT:
"Cognative degradation" is a missleading term for failure to improve on
a few measures of testing which are attention-sensitive. By that
measure, the influence of children, ringing phones, lack of sleep, and
any pleasant distraction or daydream causes temporary cognitive
degradation. But it's reversible and at these magnitudes, not clincally
relevent. Muldoon's study doesn't speak either way to this aspect
(irreversibility), since his tested people were still taking the drug.
Furthermore, far larger differences of the magnitude which Muldoon got
between his groups, can be produced by a meal or a single cup of
coffee. Making a lot of such things would be silly, and (to his credit)
Muldoon doesn't. There we are.
> The statin groups
> consistently showed either a net loss in NP test scores, or a failure to
> thrive as measured against the normal placebo groups. Got that?
> PREVENTABLE MEASURABLE COGNITIVE DAMAGE AFTER ONLY SIX MONTHS ON STATINS.
COMMENT:
"Cognitive damage" is surely an inappropriate and unwarrented
description of these results, given the fact that the drugs were being
taken at the time. Damage implies a permanent effect. It is a term that
that Muldoon does not use, and does not imply. Only YOU, Sharon, have
decided that these studies mean something that the author of the
studies never suggests or implies, and in fact specifically denies.
And finally, even the small effects in these studies lack independent
confirmation. They are interesting, and that is all. I wonder if
statins don't simply cause some people to relax.
> That is my message, and my motivation. If that disturbs you, don't read my
> posts.
COMMENT:
Your message is not backed by the facts. I'm going to handle my
disturbance by simply reminding people what the facts are, every time
you distort them.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,talk.politics.medicine,sci.med.cardiology,soc.retirement
Subject: Re: stopping statins is bad for your health
Date: 9 Aug 2005 12:44:08 -0700
Message-ID: <1123616648.722742.197470@g43g2000cwa.googlegroups.com>
Jim Chinnis wrote:
> mmlevy46@hotmail.com wrote in part:
>
> >the 33% figure you quote--is that relative risk benefit or absolute
> >risk benefit? thanks
>
> Even in a study lasting a few years, it would be impossible to get
> thousands of subjects who had higher than 33% chance of a stroke
> during the study!
> --
> Jim Chinnis Warrenton, Virginia, USA
COMMENT:
Right you are. It was a relative benefit. It prevented a third of the
strokes that were set to happen, but only a small % of patients will
have second strokes, even in a secondary study.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,talk.politics.medicine,sci.med.cardiology,soc.retirement
Subject: Re: stopping statins is bad for your health
Date: 17 Aug 2005 11:47:42 -0700
Message-ID: <1124304462.619392.135380@g44g2000cwa.googlegroups.com>
Bill wrote:
> Thanks. Note, Crestor has come on the market since then and, personally, I
> would prefer to go with those that have been around longer - since there is a
> choice.
COMMENT:
Absolutely! Stick with the ones that have long track records and are
well-studied. No sense paying Pravachol or Zocor prices for a drug
which has 1/100th the number of patient-years of data. You're supposed
to be PAYING for that data when you pay for the drug. Crestor's ripping
you off in that regard, and I can't overemphasize how slimy that is. At
least Lescol tried to pass the savings from its lack of long clinical
trials, on to the customer (i.e., you got a discount for your extra
risk due to its relative lack of clinical data). By constrast, Crestor
is mostly just razzel from intermediate endpoints (cholesterol lowering
numbers), and if the stuff ends up "Baycol-ing," it will richly deserve
it.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,talk.politics.medicine,sci.med.cardiology,soc.retirement
Subject: Re: stopping statins is bad for your health
Date: 16 Aug 2005 16:11:01 -0700
Message-ID: <1124233861.195489.159710@z14g2000cwz.googlegroups.com>
george conklin wrote:
> 20+% of elderly statins takers get a diagnosis of cancer within 1 year
> following the start of statins. That has been dismissed as not 'causal'
> since it was not predicted.
No, the incidence of cancer in the statin group in this trial was 25%
greater than the placebo group. That's *quite* different from saying
20% of people got cancer.
This is the only statin trial to see a significant increase in cancer
incidence. Analysis of all statin trials together show no cancer
increase. It may be that statins increase cancer risk by 25%, but only
in older people (over age 70, which this trial looked at). OR the
cancer results in this trial may simply be a statistical fluke. We
won't know, until somebody tries to repeat it.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,talk.politics.medicine,sci.med.cardiology,soc.retirement
Subject: Re: stopping statins is bad for your health
Date: 15 Aug 2005 20:07:16 -0700
Message-ID: <1124161636.125036.312180@f14g2000cwb.googlegroups.com>
Sharon Hope wrote:
> In addition to your guess that anyone developing Parkinson's might well have
> been dropped from the study, three other possibilities come to mind:
>
> Given we know that statins unmask Parkinson's Disease, Huntington's Disease,
> and ALS, each of which has a genetic predisposition, it is possible that
> they run genetic testing to screen out any such condition prior to the
> trial.
COMMENT:
There is no genetic test for PD or ALS. Thus, it's not possible to
screen for them. Also, we don't "know" that statins "unmask" any of the
diseases you mention. There's no good evidence for that.
Other than those quibbles, this paragraph was okay.
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,talk.politics.medicine,sci.med.cardiology,soc.retirement
Subject: Re: stopping statins is bad for your health
Date: 16 Aug 2005 15:23:30 -0700
Message-ID: <1124231009.936795.311620@g47g2000cwa.googlegroups.com>
Sharon Hope wrote:
> You are simply wrong.
>
> Re: Unmasking:
> Published studies show statins unmask PD, HD, and ALS, presumably because of
> statin-enforced CoQ10 deficiency, as CoQ10 is now shown to treat symptoms of
> these diseases.
COMMENT:
While it is true that high dose CoQ10 slowed progression of Parkinson's
in one good study, this has yet to be replicated. And it does not mean
that Parkinson's disease is unmasked by statins. Somebody can claim
anything they want in an abstract, but abstacts are just pre-science.
I've presented my share of abstracts at scientific meetings, but I
think of them as just one step removed from advertising, and so does
everybody else in the scientific community. If they aren't followed by
a paper, they are pretty much useless.
We've discussed the issue of whether or not statins actually lower
CoQ10 levels enough to measure (against the backdrop of lowering LDL,
which carries 2/3rds of CoQ10). There is evidence both for and against
a real statin effect on CoQ10 in the tissues. I would surely be on high
dose CoQ10 if I had Parkinson's disease (why not? All you lose is
money), but a theory would not be enough make me stop a statin if I had
PD and otherwise had good reason to take a statin.
> http://www.coenzymeq10.it/events/pastmeeting.html
> abstracts to this effect are available for download
>
> Re: Genetics of PD:
> "Interest in the genetics of Parkinsons Disease has recently escalated with
> the identification of a Parkinsons gene. Nussbaum and Polymeropoulos,
> published in the Nov 15, 1996 issue of Science, proposed that Parkinsons
> Disease is an autosomal dominant disorder.
COMMENT:
They proposed that some *fraction* of it is. But it cannot be a large
one, since most PD does not arive against a background of clear family
history, as Huntingon's does. Parkinson's disease is like Alzheimer's
disease and breast cancer. A *small* fraction of it is certainly
genetic (two dominant and three recessive alleles have been identified
for PD, at least). However, most people with PD have NONE of these.
Whether other alleles will be indentified in the future to pick up the
rest, is unknown.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,talk.politics.medicine,sci.med.cardiology,soc.retirement
Subject: Re: stopping statins is bad for your health
Date: 17 Aug 2005 11:35:38 -0700
Message-ID: <1124303738.583700.104680@g44g2000cwa.googlegroups.com>
Sharon Hope wrote:
> Steve Harris <sbharris@ix.netcom.com> wrote in message
> news:1124231009.936795.311620@g47g2000cwa.googlegroups.com...
> >
> > While it is true that high dose CoQ10 slowed progression of Parkinson's
> > in one good study, this has yet to be replicated. And it does not mean
> > that Parkinson's disease is unmasked by statins. Somebody can claim
> > anything they want in an abstract, but abstacts are just pre-science.
> > I've presented my share of abstracts at scientific meetings, but I
> > think of them as just one step removed from advertising, and so does
> > everybody else in the scientific community. If they aren't followed by
> > a paper, they are pretty much useless.
>
>
> The abstracts are OF the PAPERS delivered at the conference.
COMMENT:
Let me explain to you how science works. Nobody delivers a "paper" at a
conference. Only talks are delivered at conferences. Most abstracts are
simply posted on a board. Some FRACTION of abstracts are accompanied by
a talk, usually 15 minutes; sometimes longer for major resuts, but
certainly in no case enough time to read a manuscript or paper, even if
you had one available (which you usually do not).
The whole POINT of abstracts is that you can get something as notes to
alert people of findings before a complete manuscript is available.
Another class of abstracts is done so you can alert the community to
findings before enough data arives to warrent submission of a full
paper, or before all the analysis and literature review is done.
In biology (as opposed to, say, physics), electronic pre-prints of
paper manuscripts which are in the process of review, or have been
accepted but not yet published, are rarely available. Occasionally
people delivering an abstract will have paper re-prints/preprints of
something published using the same data, but that's rare. If people
wanted to read that, why would they be at the conference? The paper is
on medline and in the journals.
The abstract presented at a conference is almost never the exact
abstract of ANY paper which is finally published, and every conference
abstracts appear for data on which NO paper is published. The reason
being that there's just enough data for an abstract, but not enough to
make a decent paper. Then something changes or money runs out of the
grad student or intern leaves, etc. Don't be fooled by the fact that
the same word "abstract" is used BOTH for the thing you download on
medline, and the thing you see typed up as being presented at a
conference. Almost always they are NOT the same thing, and in many
cases there's no correspondance at all.
If these are abstracts of actual published papers (going back to 2001),
as you say, then where are the papers? They should be out by now. If
you can't find them, that makes my point. If you can, post the medline
locator number.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.radiology,sci.med,sci.med.nursing
Subject: Re: Question about radiologists comments. (What does this mean?)
Date: 17 Aug 2005 16:53:49 -0700
Message-ID: <1124322829.508882.82350@g44g2000cwa.googlegroups.com>
Howard McCollister wrote:
> <fresh~horses@despammed.com> wrote in message
> news:1124320080.351213.218100@o13g2000cwo.googlegroups.com...
> > The cite for statin induced pancreatitis. Zee
> >
> >
> > http://www.joplink.net/prev/20 0507/11.html
> >
> > Full text available free, a letter to the editor
> >
> > JOP. J Pancreas (Online) 2005; 6(4):380.
> >
> > Drug Induced Pancreatitis Might Be a Class Effect of Statin Drugs
> >
> > Sonal Singh
> >
> > "Clinicians need to be aware that drug induced pancreatitis might be a
> > class effect of statin drugs and the newest statin, rosuvastatin is as
> > likely to be associated with pancreatitis as the other statins."
> >
>
>
> Totally irrelevant to the discussion regarding gallstones. A surgeon would
> not remove your gallbladder for drug or chemical induced pancreatitis.
>
> HMc
COMMENT:
Not only that, but this whole argument that statins cause pancreatitis
is based on reports of TWO patients who got pancreatitis while taking
one statin, then later got pancreatitis again while taking another. Duh.
I've got a newsflash: pancreatitis happens often enough that every
doctor has seen at least dozens and probably hundreds of cases, and
it's more common in the kind of people who take statins (obese
diabetics with high triglycerides-- who are also--- surprise the people
who make gallstones). If you've been on one statin, your doctor is
likely to switch you to another, if something funny happens. But now
the rub: people who've had one bout of pancreatitis are likely to have
another one, and that was true before statins were invented. And if
they do these days, they'll still be on that second statin. What do you
do then? Why, blame the whole CLASS of drugs, apparently. On the basis
of N=2 patients. Sweet.
And I suppose if they stopped the statins altogether in favor of
another anticholesterol drug, and the patient got pancreatitis *again,*
they could hypothesize a general "anti-cholesterol drug pancreatitis."
From there we go to an "general medication pancreatitis", a
"hospitalization pancreatitis," and "fengshuious pancretitis" cause by
bad couch placement and bad window treatments, and finally (if
necessary) a terraneo-pancreatitis, caused by the gross effects of
living on this imperfect orb. That's a toughie, because your control
group has to be in orbit.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.nutrition
Subject: Re: They just finished doubling (corrupt) NIH funding over the last
five years
Date: 14 Aug 2005 12:38:11 -0700
Message-ID: <1124048291.241832.110840@z14g2000cwz.googlegroups.com>
Robert wrote:
> FDA panel says no to over-the-counter statin drugs; will the
> recommendation stand?
> Merck and Johnson & Johnson are working hard to make statin drugs available
> without a prescription. The thought is downright horrifying to those who
> know the true dangers of statin drugs -- muscle wasting, brain fog, even the
> risk of birth defects -- but it's just "business as usual" at Big Pharma.
> The pharmaceutical industry has been selling so many dangerous drugs to so
> many people for so long, that adding another over-the-counter medication to
> the mix didn't seem like such a big deal, apparently.
COMMENT:
It's worth noting that we have an over the counter statin NOW. It's
called red rice yeast (the red coloring of Peking Duck), and it
contains mevastatin (Mevacor), which was originally a natural product,
like penicillin. At 4 capsules a day you can get pharmacologic doses of
the stuff and lower your cholesterol quite a lot. I haven't heard much
screaming and carrying on about this stuff yet, probably because it
sounds so benign. RED RICE YEAST, THIEF OF MEMORY! Doesn't sound like a
best seller. "Peking Duck Cause You to Lose Your Mind, Say Traditional
Chinese." Riiiiight.
As for statins causing "brain fog" it's must be very rare if it
happens. A lot rarer than brain fog from OTC antihistamines or OTC
beer. Stop the hysteria, folks. Sheesh.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,sci.med.cardiology
Subject: Re: Harris, McCollister, Rind
Date: 21 Aug 2005 15:00:59 -0700
Message-ID: <1124661659.286324.208390@o13g2000cwo.googlegroups.com>
David Rind wrote:
> I don't see what that has to do with the truth of my statements that HPS
> included lots of people over age 70 and found no increase in mortality
> or cancer.
COMMENT
But we must wonder in fairness if they were merely diluted out, unless
HPS actually looked at cancer rates in their over-70 subset. Did they?
If they did, I haven't been able to find it, and I looked.
I don't think this is real effect in PROSPER either, for reasons
explained in other messages. But it would be nice if somebody in other
trials broke out some data to answer these questions.
Here's another: The Walsh JAMA paper last year which meta-analyzed and
found a remarkable overall mortality RR of 1.00 (95% CI, 0.77-1.29) for
statin treatment for women even in SECONDARY prevention. Not even a
trend down. This is more than 8,000 women, a meta-group for which the
reduction in CARDIAC mortality was a barely significant, but still
stignificant RR 0.74 (95% CI, 0.55-1.00) with more significant
endpoints on all cardiac event risks. So now I ask: If a drug can
reduce cardiac mortality by a quarter, even with the endpoints from .55
to 1.00, then how can there not be even TREND seen in total mortality,
given that cardiac mortality is, or should be, more than half of total
mortality? It might not be significant anymore, but it should SHOW.
There's something very fishy here in this meta-analysis which begs to
be teased out. Something else causing mortality has got to give, so
that there's at least a big *trend* toward non-cardiac mortality
somewhere, to make up for the numbers here. Has to be. So inquiring
minds want to know: where is it?
SBH
JAMA. 2004 May 12;291(18):2243-52.
Drug treatment of hyperlipidemia in women.
Walsh JM, Pignone M.
Division of General Internal Medicine and Department of Epidemiology and
Biostatistics, University of California, San Francisco, USA.
jmwalsh@itsa.ucsf.edu
CONTEXT: Several clinical trials have evaluated the effects of
lipid-lowering medications on coronary heart disease (CHD). Many of the
trials have not included enough women to allow sex-specific analyses or
have not reported results in women separately. OBJECTIVES: To assess and
synthesize the evidence regarding drug treatment of hyperlipidemia for
the prevention of CHD events in women and to conduct a meta-analysis of
the effect of drug treatment on mortality. DATA SOURCES: We searched
MEDLINE, the Cochrane Database, and the Database of Abstracts of Reviews
of Effectiveness for articles published from 1966 through December 2003.
We reviewed reference lists of articles and consulted content experts.
STUDY SELECTION AND DATA EXTRACTION: Studies of outpatients that had a
treatment duration of at least 1 year, assessed the impact of lipid
lowering on clinical outcomes, and reported results by sex were included.
Outcomes evaluated were total mortality, CHD mortality, nonfatal
myocardial infarction, revascularization, and total CHD events. Summary
estimates of the relative risks (RRs) with therapy were calculated using
a random-effects model for patients with and without a previous history
of cardiovascular disease. DATA SYNTHESIS: Thirteen studies were
included. Six trials included a total of 11 435 women without
cardiovascular disease and assessed the effects of lipid-lowering
medications. Lipid lowering did not reduce total mortality (RR, 0.95; 95%
confidence interval [CI], 0.62-1.46), CHD mortality (RR, 1.07; 95% CI,
0.47-2.40), nonfatal myocardial infarction (RR, 0.61; 95% CI, 0.22-1.68),
revascularization (RR, 0.87; 95% CI, 0.33-2.31), or CHD events (RR, 0.87;
95% CI, 0.69-1.09). However, some analyses were limited by too few CHD
events in the available trials. Eight trials included 8272 women with
cardiovascular disease and assessed the effects of lipid-lowering
medications. Lipid lowering did not reduce total mortality in women with
cardiovascular disease (RR, 1.00; 95% CI, 0.77-1.29). However, lipid
lowering reduced CHD mortality (RR, 0.74; 95% CI, 0.55-1.00), nonfatal
myocardial infarction (RR, 0.71; 95% CI, 0.58-0.87), revascularization
(RR, 0.70; 95% CI, 0.55-0.89), and total CHD events (RR, 0.80; CI,
0.71-0.91). CONCLUSIONS: For women without cardiovascular disease, lipid
lowering does not affect total or CHD mortality. Lipid lowering may
reduce CHD events, but current evidence is insufficient to determine this
conclusively. For women with known cardiovascular disease, treatment of
hyperlipidemia is effective in reducing CHD events, CHD mortality,
nonfatal myocardial infarction, and revascularization, but it does not
affect total mortality.
Publication Types:
Meta-Analysis
Review
PMID: 15138247 [PubMed - indexed for MEDLINE]
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med,sci.med.cardiology
Subject: Re: Harris, McCollister, Rind
Date: Sun, 21 Aug 2005 22:24:12 -0400
Message-ID: <debd0i$pha$1@reader2.panix.com>
Steve Harris wrote:
> David Rind wrote:
>
>>I don't see what that has to do with the truth of my statements that HPS
>>included lots of people over age 70 and found no increase in mortality
>>or cancer.
>
>
> COMMENT
>
> But we must wonder in fairness if they were merely diluted out, unless
> HPS actually looked at cancer rates in their over-70 subset. Did they?
> If they did, I haven't been able to find it, and I looked.
>
> I don't think this is real effect in PROSPER either, for reasons
> explained in other messages. But it would be nice if somebody in other
> trials broke out some data to answer these questions.
>
> Here's another: The Walsh JAMA paper last year which meta-analyzed and
> found a remarkable overall mortality RR of 1.00 (95% CI, 0.77-1.29) for
> statin treatment for women even in SECONDARY prevention. Not even a
> trend down. This is more than 8,000 women, a meta-group for which the
> reduction in CARDIAC mortality was a barely significant, but still
> stignificant RR 0.74 (95% CI, 0.55-1.00) with more significant
> endpoints on all cardiac event risks. So now I ask: If a drug can
> reduce cardiac mortality by a quarter, even with the endpoints from .55
> to 1.00, then how can there not be even TREND seen in total mortality,
> given that cardiac mortality is, or should be, more than half of total
> mortality? It might not be significant anymore, but it should SHOW.
> There's something very fishy here in this meta-analysis which begs to
> be teased out. Something else causing mortality has got to give, so
> that there's at least a big *trend* toward non-cardiac mortality
> somewhere, to make up for the numbers here. Has to be. So inquiring
> minds want to know: where is it?
>
> SBH
I had the same questions prior to the HPS all-cause mortality subset
analyses (which were not published in the original paper). As a result
of these issues being raised in this group, I wrote to the HPS
investigators in February of this year and was told that they would be
publishing the subset analyses a few weeks later. These were published
in BMC Medicine in March:
TI - The effects of cholesterol lowering with simvastatin on
cause-specific mortality and on cancer incidence in 20,536 high-risk
people: a randomised placebo-controlled trial [ISRCTN48489393].
SO - BMC Med 2005 Mar 16;3(1):6.
This paper found the results I stated above in the subset of those over
the age of 70 and also in women: all-cause mortality followed
cardiovascular mortality, looked just like the results in younger people
and in men, and there was no evidence of an increase in noncardiac
mortality in general or cancer in particular.
So overall, this was a very reassuring paper about the benefits of statins.
--
David Rind
drind@caregroup.harvard.edu
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,sci.med.cardiology
Subject: Re: Harris, McCollister, Rind
Date: 21 Aug 2005 20:28:10 -0700
Message-ID: <1124681289.987406.88770@g49g2000cwa.googlegroups.com>
David Rind wrote:
> I had the same questions prior to the HPS all-cause mortality subset
> analyses (which were not published in the original paper). As a result
> of these issues being raised in this group, I wrote to the HPS
> investigators in February of this year and was told that they would be
> publishing the subset analyses a few weeks later. These were published
> in BMC Medicine in March:
>
> TI - The effects of cholesterol lowering with simvastatin on
> cause-specific mortality and on cancer incidence in 20,536 high-risk
> people: a randomised placebo-controlled trial [ISRCTN48489393].
> SO - BMC Med 2005 Mar 16;3(1):6.
>
> This paper found the results I stated above in the subset of those over
> the age of 70 and also in women: all-cause mortality followed
> cardiovascular mortality, looked just like the results in younger people
> and in men, and there was no evidence of an increase in noncardiac
> mortality in general or cancer in particular.
>
> So overall, this was a very reassuring paper about the benefits of statins.
>
> --
> David Rind
> drind@caregroup.harvard.edu
COMMENT:
Aha! And here it is. This pretty much nails the question on cancer,
older people, and secondary prevention of death in women (ie women with
vascular disease or diabetes). At least for Zocor. Too bad this isn't
for my favorite drug Pravachol. I may have to switch now. But if all
this is true for the most invasive and lipiphilic of the old statins, I
suspect pravachol is still safe. I only worry about effects like cancer
on the liver, the only place pravachol certainly goes (and perhaps more
so) than Zocor.
BMC Med. 2005 Mar 16;3(1):6.
The effects of cholesterol lowering with simvastatin on cause-specific
mortality and on cancer incidence in 20,536 high-risk people: a
randomised placebo-controlled trial [ISRCTN48489393].
Heart Protection Study Collaborative Group.
BACKGROUND: There have been concerns that low blood cholesterol
concentrations may cause non-vascular mortality and morbidity.
Randomisation of large numbers of people to receive a large, and
prolonged, reduction in cholesterol concentrations provides an
opportunity to address such concerns reliably. METHODS: 20,536 UK adults
(aged 40-80 years) with vascular disease or diabetes were randomly
allocated to receive 40 mg simvastatin daily or matching placebo.
Prespecified safety analyses were of cause-specific mortality, and of
total and site-specific cancer incidence. Comparisons between all
simvastatin-allocated versus all placebo-allocated participants (ie,
"intention-to-treat") involved an average difference in blood total
cholesterol concentration of 1.2 mmol/L (46 mg/dL) during the scheduled
5-year treatment period. RESULTS: There was a highly significant 17% (95%
CI 9-25) proportional reduction in vascular deaths, along with a
non-significant reduction in all non-vascular deaths, which translated
into a significant reduction in all-cause mortality (p = 0.0003). The
proportional reduction in the vascular mortality rate was about one-sixth
in each subcategory of participant studied, including: men and women;
under and over 70 years at entry; and total cholesterol below 5.0 mmol/L
or LDL cholesterol below 3.0 mmol/L. No significant excess of
non-vascular mortality was observed in any subcategory of participant
(including the elderly and those with pretreatment total cholesterol
below 5.0 mmol/L), and there was no significant excess in any particular
cause of non-vascular mortality. Cancer incidence rates were similar in
the two groups, both overall and in particular subcategories of
participant, as well as at particular primary sites. There was no
suggestion that any adverse trends in non-vascular mortality or morbidity
were beginning to emerge with more prolonged treatment. CONCLUSION: These
findings, which are based on large numbers of deaths and non-fatal
cancers, provide considerable reassurance that lowering total cholesterol
concentrations by more than 1 mmol/L for an average of 5 years does not
produce adverse effects on non-vascular mortality or cancer incidence.
Moreover, among the many different types of high-risk individual studied,
simvastatin 40 mg daily consistently produced substantial reductions in
vascular (and, hence, all-cause) mortality, as well as in the rates of
non-fatal heart attacks, strokes and revascularisation procedures.
PMID: 15771782 [PubMed - in process]
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,sci.med.cardiology
Subject: Re: Harris, McCollister, Rind
Date: 21 Aug 2005 16:14:06 -0700
Message-ID: <1124666046.338775.310280@o13g2000cwo.googlegroups.com>
listener wrote:
> HPS was an important study.
>
> With a two-thirds compliance rate, simvastatin significantly reduced
> total mortality by 12% (12.9% vs 14.6%; p<0.001) and was even efficacious
> against vascular mortality with a 17% reduction rate (7.7% vs 9.2%; p
> <0.0002).
>
> There was a nonsignificant but slightly favorable trend in reduction of
> nonvascular mortality, but no evidence of hazard on any particular
> nonvascular cause of death, including cancer.
>
> Overall, patients experienced a 27% reduction in stroke risk (4.4% vs
> 6.0%; p<0.00001), most prominently in ischemic stroke, but no excess
> hemorrhagic stroke.
>
> In terms of all major vascular events, researchers again found a
> significant 24% reduction in total CHD, total stroke, and
> revascularization (19.9% vs 25.4%; p<0.00001).
COMMENT:
Yes. People in this study did better than most of the meta-analyses,
and this one study had more people than many meta-analyses, also.
Finally, the statistical power needed in a single study and this one's
a monster. So now the problem is which to believe. If you distrust drug
companies and all the separate investigators involved in analysis of
this particular study, then you're not going to believe them, even if
they do report a significant decrease in total mortality.
But as you point out, when the disenters get down to needing conspiracy
theories to explain the published stuff, it's all up. There's no use
arguing with such people.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,sci.med.cardiology
Subject: Re: Harris, McCollister, Rind
Date: 21 Aug 2005 16:03:27 -0700
Message-ID: <1124665407.834141.236020@g44g2000cwa.googlegroups.com>
fresh~horses@despammed.com wrote:
> http://www.medicalconsumers.org
> Meeting of the Institute of Medicine 's (IOM's) Committee on the
> Assessment of the US Drug Safety System, July 19, 2005.
> Not specifically about cancer and statins, but addressing why we can't
> trust the information:
> Maryann Napoli, Center for Medical Consumers, New York City
>
> "I have been a consumer advocate for nearly 30 years, writing about
> medical research and critically appraising clinical trials. I'm still
> surprised that I could have been at it so long without fully
> understanding-until about two years ago-that it is not unusual for
> drug company-sponsored trials to withhold data about adverse drug
> reactions. I am referring to trials published in high-profile medical
> journals.
>
> I learned this while writing about the cholesterol-lowering drugs,
> statins, when I was putting together a poster for the Cochrane
> Collaboration's 2003 conference. My work has long focused on the
> selling of drugs to healthy people-drugs to reduce a risk factor,
> drugs that healthy people will take for the rest of their lives. I have
> always been interested in the way we Americans have come to accept the
> idea that a risk factor should be treated as if it were a disease.
> Bisphosphonate drugs for bone loss, postmenopausal estrogen to improve
> lipid profiles-that sort of thing. The emphasis-when selling
> healthy people the idea of lifelong preventive drug therapy-is on the
> benefits. We don't hear much about the drugs' risks.
>
> For my Cochrane Poster, I summarized the proven benefits of statins for
> people who do not have heart disease-just a few risk factors like
> high cholesterol. I found only one review of the five major mostly
> primary prevention trials that had compared a statin drug with a
> placebo. All five were drug company-sponsored and published in leading
> medical journals. Here's what jumped out at me. The authors of that
> review, who are based at the University of British Columbia , wrote in
> their on-line publication, Therapeutics Initiative, that only two of
> the five trials had reported their serious adverse events (SAE). The
> UBC authors reported that they had asked the investigators from other
> three trials for their SAE data and were refused. Working with what
> they had (data from only two of the trials), the UBC authors found that
> the benefit of statins was far more modest than doctors and the general
> public have been led to believe. There was approximately a 1.8% lower
> rate of non-fatal heart attacks in the male study participants, but
> this was offset by the 1.4% increase in SAE among the statin users. SAE
> were defined as "any untoward occurrence that results in death, is
> life-threatening, requires hospitalization or results in prolonged
> hospitalization, or significant disability." [1]
COMMENT:
And right there we come to a real problem, which I've pointed out
before. This SAE list includes ANYTHING that gets you into a hospital.
And since it's appropriate to hospitalize many people for things much
less serious than a heart attack, and since every doctor has done so,
it's hardly fair to fold this in with heart attack statistics,
subtracting one from the other. It would be more appropriate if they'd
dropped that one criterion, and kept the others (which are more
comparable). Otherwise, we don't know if we're subtracting MI's from
dizzy-spells or chest pains that turned out to be nothing, or what.
Perhaps I'll write to the British Columbia peole if they will give me
THEIR sub-set data, with the one-day hospitalizations and non-serious
events removed. Hey, does this mean I can't THEM because they analyzed
ther data in a way *I* don't like? Hmmmmm.
> It troubled me to see that statins aren't anywhere near the lifesaving
> medications they're purported to be. In fact, this review showed that
> for primary prevention, only middle-aged men under 70 benefited from
> these drugs. Not only was the benefit small, it was canceled by the
> risks.
Bzzt. The decreased risk of dying was "cancelled" by the excess risk of
hospitalization? I don't think so.
>But it was far more alarming to learn that we do not have the
> full story on the safety of statins because three of the trials had
> refused to release all their SAE data [2] ...so it is quite possible
> that the risks could considerably outweigh the benefits.
COMMENT:
Except in the case of mortality, as pointed out.
As for the rest, as I've said before, I think it is somewhat irregular
and maybe even irreponsible to suggest that a drug which has the same
patient dropout rate as placebo in studies (usually about 1 or 2%), has
some horrid effect on quality of life as to compensate for the 1 or 2%
of people for which it prevents a stroke or heart attack. To me, this
seems highly unlikely. Can the reader thing of any scenario in which it
is true? I invite comments.
> How can healthy people who are on lifelong drug therapy make an
> informed decision about their medications when drug companies are
> allowed to withhold such important information? To go beyond statins
> for a moment, I've found that it is not unusual for anti-hypertensive
> drug trials to show that the cardiovascular death rate is reduced by
> the drug. But the overall death rate is no different from that of
> placebo group. Often this finding goes unexplored.
COMMENT:
Usually it doesn't need to be. Since cardiovascular death rate should be
roughly half of total deaths (or even less if you subtract out the
nonautopsied people who died in their sleep, or had a dysrhythmia when
septic, etc and got coded as cardiac deaths), the problem needs
"explaining" only when cardiovascular death rate is significantly down
without even a downward trend in overall mortality (ie, you expect a
severe statistical diluting effect, but not a complete one). This
happens rarely, but it does happen. In these cases, I certainly agree
with Ms. Napoli, the writer.
SBH
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Low Dose Lipitor & Zocor Triggered Muscle Pain - What's Next?
Date: Tue, 23 Aug 2005 22:21:14 -0400
Message-ID: <deglj1$p7d$1@reader2.panix.com>
jay1000 wrote:
> OK - Gave it a try but both Lipitor 5 mg and Zocor 10 mg caused muscle
> twitching and pain. I really NEED an atherosclerosis risk reduction plan.
> I have an appointment with my doctor in a week and presumably he will have a
> plan. But if he doesn't, I want something to suggest and this is my best
> shot.
>
> Would appreciate any comments...hopefully constructive.
>
> Background:
>
> 1. I am in the high risk category with four very old bypasses.
> 2. Have been on various statins for about 17 years...since the first one was
> approved.
> 3. Recently developed muscle twitching and pain when Lipitor was increased
> from 10 to 20 mg
> 4. Muscle Problems disappeared after discontinuing Lipitor - only took about
> three days
> 5. I have since tested Lipitor 5 mg and Zocor 10 mg and muscle problems do
> reoccur so Lipitor and Zocor are unusable.
> 6. Currently on a low-fat diet with fish instead of meat or chicken
> 7. Exercise daily
> 8. Currently take Questran, CoQ10, Policosanol,
>
> Proposed Plan - (if my doctor agrees):
>
> 1. Start with Pravachol 5 mg
> 2. Lipid test every 6 weeks
> 3. If LDL > 100 increase Pravachol by 5 mg
> 4. Keep repeating steps 2 & 3 until either the Pravachol dose reaches 20 mg,
> LDL < 100 or until there are muscle problems, whichever is first.
> 5. If Pravachol unsuccessful because of muscle problems, discontinue
> Pravachol and start Niaspan
> 6. If no muscle problems but Pravachol dose is 20 mg and LDL > 100, hold at
> 20 mg Pravachol and start Niaspan. Note: I am not happy with this step as
> combining statin and niacin can promote rhabdomyolysis and presumably non-
> rhabdomyolysis muscle problems. Might be better to keep increasing
> Pravachol or drop Pravachol and switch to Niaspan?
>
> Excluded Treatments:
>
> 1. Lipitor and Zocor - they both cause me muscle problems
> 2. Fibrates - increased risk of cancer, pancreatitis (inflammation of the
> pancreas), gallstones, and problems from gallstone surgery; most
> importantly, they caused an overall increase in mortality.
> 3. Zetia - "So far, reported side effects seem to be few and mild, but a
> recent analysis of FDA data by Public Citizen revealed serious adverse
> effects with Zetia involving muscle, liver and other organ systems. Public
> Citizen advises against the use of Zetia, especially in combination with a
> statin."
> 4. Inositol Hexaniacinate (alternative to Niaspan) - no data on cholesterol
> control effectiveness. No way of ensuring quality of product as it is
> available only as a dietary supplement.
The overally proposed scheme seems to have been written by someone who
has looked at the evidence and made reasonable decisions. I'll make a
few general comments since it's generally hard to give useful specific
advice over the net.
1) Pravastatin appears less likely to cause muscle problems than most
other statins. I'm not sure that I see much advantage to going up on the
dose in tiny increments however. It should be relatively easy to figure
out a dose that would be expected to reduce the LDL down a given amount
in someone who has been on other statins previously.
2) While there's some value to an LDL target like <100 mg/dL in someone
at high risk for cardiovascular events, being on some statin is probably
quite beneficial even if that goal is not achieved.
3) I'm not a fan of Zetia given the absence of data on clinical
outcomes, but my sense is that Public Citizen tends to go overboard when
they dislike a drug and tends to recommend against drugs without any
seeming ability to consider balancing benefits against risks. I would
not eliminate it as an option in someone who has known CHD and cannot
tolerate statins.
4) I don't know of any particular reason to start adding niacin once a
pravastatin dose of 20 mg has been reached if the pravastatin isn't
causing side effects.
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Low Dose Lipitor & Zocor Triggered Muscle Pain - What's Next?
Date: Wed, 24 Aug 2005 07:23:36 -0400
Message-ID: <dehlbu$q6j$1@reader2.panix.com>
jay1000 wrote:
> I plotted the Pravachol LDL reduction data and it looks like there is an
> inflection point at about 20 mg. That's not a strong reason to stop at 20
> mg but it does say you get less LDL reduction per mg at doses over 20 mg.
> What I have never seen is data on adverse effects as a function of dose. I
> suspect that there is also a point of inflection but I bet the slope goes
> the other way.
You may be right about the inflection point, but the comparative statin
study I've tended to look at for such information doesn't seem to show this.
Take a look at:
Jones, P, Kafonek, S, Laurora, I, et al for the CURVES Investigators.
Comparative dose efficacy study of atorvastatin versus simvastatin,
pravastatin, lovastatin, and fluvastatin in patients with
hypercholesterolemia (the CURVES study). Am J Cardiol 1998; 81:582.
LDL lowering with 40 mg of pravastatin continued down on the trend you
would expect after 10 mg and 20 mg.
--
David Rind
drind@caregroup.harvard.edu
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Cognitive problems with simvastatin?
Date: 30 Aug 2005 13:29:48 -0700
Message-ID: <1125433788.319471.103770@g43g2000cwa.googlegroups.com>
bigjon wrote:
> Ask your doctor about Fibrates or Bezafibrates, they do a better job on the
> triglycerides (VLDL-triglycerides, VLDL-cholesterol, LDL-cholesterol,
> HDL-cholesterol)and with no major side effects. All I know to be wary of
> with them is Hepatic or renal dysfunction, including primary biliary
> cirrhosis, or a Pre-existing gallbladder disease...
>
> Jon
> Not a Dr.
> A former Statin Victim
COMMENT:
And not a very good advice-giver. Taking a fibrate is out of the frying
pan and into the fire. All the criticisms leveled at statins which
turned out not to be true of statins (increased cancer in human
studies, no decrease in cardiac mortality, no decrease in total
mortality), actually ARE true of fibrates. It's extremely ironic that
we should have people recommending fibrates over statins on the basis
of non-primary and intermediate endpoints, like lipid changes. That was
the argument used for the statins before the really big study results
came in, and you-all had no problem finding the logical and clinical
problem with that kind of thinking. How now?
If you've had brain problems you think are due to a statin, take
pravachol which doesn't get into the brain. According to the
literature, there is little difference between first-generation statins
in their propensity to cause rhabdomyolysis, but I cannot find any
primary evidence that this is actually true. Pravachol muscle problems
are limited to a few case-reports, and are not very believable.
Pravachol actual package insert warnings are based on muscle problems
from the statin CLASS, not problems with pravachol itself in the 4S,
WOSCOPS or PROSPER trials. In WOSCOPS the *total* mortality reduction
due to pravastatin was 22-24%, more or less in line with the reduction
seen with simvastain in HPS. Ask your doc to find you similar
statistics for any fibrate. So what if he has Tricor from the drug rep?
Are you grown-up enough to know what that means?
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Cognitive problems with simvastatin?
Date: 30 Aug 2005 15:46:46 -0700
Message-ID: <1125442006.346737.53840@f14g2000cwb.googlegroups.com>
Robert wrote:
> Fibrates as BigJon mentioned is still being used but I would be more
> favorable to Niacin (nicotinic acid).
> The problem is the getting down the triglycides and after reaching LDL goals
> obtaining Non-HDL goals of <130 or <160 or <190 depending on risk category.
That's what fish oil is for. Do not use fibrates until 10 grams a day
of fishoil (which can be taken all at once) fails.
> With ATPIII we have statins followed by fibrates or nicotinic acid to obtain
> Non-HDL goals after LDL goals are met.
COMMENT:
ATPIII is (sorry to say) biased by drug-company financed literature
reviews. There is plenty of good data in the peer-reviewed literature
on fish oil as a triglyceride reducer of considerable power. I use it
that way myself, and I've seen it fix fasting triglycerides as high as
1400 (which looks like milk when you spin the tigertop down). I haven't
been forced to use a fibrate yet. I would, if I had to, but so far, am
home free.
Naturopathically,
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Statin drugs lower heart attack death-study
Date: 30 Aug 2005 18:06:18 -0700
Message-ID: <1125450378.187257.151940@g44g2000cwa.googlegroups.com>
Bill wrote:
>
> To me, anyway, it is important to understand why something happens - not just
> that it happens. Also, understanding this could help with ways to refine the
> treatment, what and what not to combine it with, and when not to apply it.
>
> It might also help our understanding of why statins work in general and that
> could help us better define the sets of people it should and should not be
> given to.
>
> Bill
COMMENT:
Of course I don't know the answer. If you like hypotheses to comfort
you until the truth comes in, I can throw them out as well as the next
guy. For one thing, we know that LDL-C is directly thromogenic. Your
risk of MI goes up for a few hours, even after you eat a high-fat meal.
There is some evidence that statins are anti-thomobogenic, inhibiting
DVT, for example (which happen in veins and therefore have nothing to
do with atherosclerosis).
Other mechanisms have been mentioned: statins attenuate all kinds of
cell-cell adhesion, including platelet and lymphocyte sticking.
Isoprenylation is a ubiquitous cellular switch and is probably involved
in some of this. If you can't reduce HMG-CoA you can't make
isoprenyl-PP.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: CABG Alzhelimer's Study
Date: 30 Aug 2005 15:25:27 -0700
Message-ID: <1125440727.299469.238950@g49g2000cwa.googlegroups.com>
Sharon Hope wrote:
> Jim,
>
> Your point that there is only a small difference in some of the tests is
> well taken, but the study gave a snapshot at 6 months of a drug that is
> supposed to be taken for life.
>
> I know, because I have seen it, that the deficit increases with time on the
> treatment. This is an early warning test.
>
> When you live with a high-achieving high-functioning type-A who degrades
> during 4 years of Lipitor to below the 1percentile, there is no doubt that
> at 6 months there was no 'meaningful' loss, but a measurable loss. Had we
> had a test to warn at 6 months that the damage was already under way, that
> would have been 'significant' information, even if the cognitive damage at
> that time was not considered 'significant.'
>
> Now, after 3 + years off the Lipitor and cognitive rehabilitation therapy,
> it is 'impaired.'
>
> Preventable life-altering damage, for which we did not have the luxury of
> early warning. Now that early warning is on record - in 3 different tests
> during 2 different trials.
COMMENT:
The problem is that no such thing as you describe has been seen in any
statistically significant way in the HPS and PROSPER controlled trials
which have looked for cognitive decline in statin users in very large
numbers of people (5,800 and 20,000) over periods on the order of 3
years.
It's amazing the contortions that anti-statin people have gone to, in
order to explain the large-trial results away. For example:
http://www.geriatrictimes.com/g040618.html
Here Dr. B. Golomb suggests that the telephone mental status interview
in the HPS might have missed subtle changes in visual spatial
functioning. To which I reply: "Maybe so, but we're talking about
people crippled with global amnesia, and suffering major significant
mental status losses that result in lost jobs and so on." So it's not
the same thing. The switching of categories happens regularly---
anti-statin crusaders will tell your horror stories of people "severely
impaired" and mis-diagnosed with Alzheimer's disease due to "statin
dementia", and then their professional backers will wimp out and tell
you that such things it might have been missed on a telephone interview
in the largest trial available. As a trained and board-certified
geriatrician (which Dr. Golomb is not) I can tell you that THAT is not
likely.
(In fact, my recommendation for Dr. Golomb before she writes such
drivel for the Geriatric Times, is that she actually practice
geriatrics for a few years and spend some time evaluating people who
actually ARE demented. She has a Ph.D. in "neurobiology" but spent it
doing image recognition A.I. computer systems, and obviously it didn't
prepare her much for the clinical swamp she's stuck her foot in. But it
looks good on her C.V., I admit).
Dr. Golomb's second argument for the HPS study results is that perhaps
all the people who were going to suffer statin mental problems might
have washed out in the first six weeks in the washout phase of the
trial, and that's why the rest of the patients went 3 years with no
detectable major mental problems, even though regularly screened for
them. That's a fine suggestion, but again hardly squares with reports
of slow and progressive statin impairment for which minor problems even
at 6 months, are just a "snapshot" and harbinger of far worse problems
to come, after a couple of years of statin use. Dr. Golomb's argument
certainly argues AGAINST such a scenario. Nice try, though.
My favorite Golomb argument (see cite above, in the Geriatric Times) is
that since statins decrease stroke and death, and stroke decreases
mental status, and death removes people who might be alive to show
decreased mental status, that maybe these two effects exactly
compensate for a direct drug-induced dementia in statin takers. An
argument which only has three problems:
1) Even if it were true, by intention to treat, if you didn't want to
be demented or suffer decreased mental status for any reason, you would
still have no reason to fear statins, since you will be just as
demented if you take them than if you don't (albeit for different
reasons). This is especially true of people taking statins for cardiac
reasons, who wonder about their brains. The answer from the big trials
is that the net effect is at least zero.
2) The small absolute numbers of decreased strokes and deaths in these
studies make it extremely unlikely that even if every dead person had
been saved into a state of dementia, and every extra stroke person had
been demented because of the stroke, that even THIS would have affected
the average mental status scores of thousands of people. Sorry, not
likely.
3) Finally, and best, is that the trial design for both HPS and PROSPER
makes 1) and 2) impossible anyway. Stroke in both trials removed people
from the study, and mental status testing points were compared only for
patients *still enrolled in the trial,* which by definition means in
people who had not been diagnosed with a new stroke (obviously this
also applies to people who died in the trial). Dr. Golomb made a major
error, there.
Steve Harris, M.D.
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: CABG Alzhelimer's Study
Date: 30 Aug 2005 20:06:43 -0700
Message-ID: <1125457603.434687.148100@g47g2000cwa.googlegroups.com>
Sharon Hope wrote:
> Well, her CV is far more impressive than - oh, wait, is YOUR CV online?
No, and for good reason. I will admit that Dr. Golomb is a far better
self-promoter than I am. Anybody who testifies before congress on Gulf
War syndrome. Gosh, you have to be impressed.
> And, she can spell her name, which you don't seem to be able to do.
Well, hell, considering it's her name and not mine, THAT'S an
impressive skill.
> And, she does practice, and with live patients, which you apparently do not.
I do still practice. Don't let me josh you.
> I will continue to listen to anything she has to say.
>
> When the NIH decides to fund you to be the principal investigator in
> something, anything, I might then take your input seriously.
LOL. No, you won't. You don't have any higher opinion of the NIH than I
do. The difference is, I'm honest about it and you're not. You're just
pretending you do at the moment, for purposes of argument, because it
suits your point at the moment.
Shame on you.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: CABG Alzhelimer's Study
Date: 30 Aug 2005 17:13:10 -0700
Message-ID: <1125447190.078228.286140@f14g2000cwb.googlegroups.com>
zee wrote:
> Steve Harris wrote:
> > http://www.geriatrictimes.com/g040618.html
> >
> > Here Dr. B. Golomb suggests that the telephone mental status interview
> > in the HPS might have missed subtle changes in visual spatial
> > functioning. To which I reply: "Maybe so, but we're talking about
> > people crippled with global amnesia, and suffering major significant
> > mental status losses that result in lost jobs and so on." So it's not
> > the same thing.
>
>
> Can you read? "Subtle changes in visual spatial reasoning."
COMMENT:
I can read, thanks. (Though I'm not so sure about you or Dr.
Golomb....) Subtle changes are subtle changes. You might miss them on a
phone interview, but that doesn't get you out of the conclusion that
any changes (if any) are at worst, *subtle.*
> Crippled with global amnesia...did you think we would have an episode
> on the phone to demonstrate for you? It is "transient". Not often
> observed, but let me tell you, misunderstood by our physicians and
> ourselves.
COMMENT:
Umm, it's transient and you don't remember even having HAD it? So can't
*report* it, when asked? That does NOT sound like your descriptions, or
Ms. Hope's, or (for that matter) Dr. Graveline's. Did he write that
book about what other people said he did, that he can't remember doing,
like sleepwalking? No.
Look, episodes of partial amnesia of one kind or another used to be
called "absent mindedness", so long as they didn't badly interfere with
day to day functioning and tasks at hand (like various mental status
tests, including those done by phone). And sometimes, even if they did.
One of the more famous mathematicians of the last century, John Von
Neumann, a man kept busy consulting for the military, Los Alamos, and
many academic institutions, once called up his wife and said "Could you
tell me why I'm in New York, please?" And this man who was at home in
the most abstract of mathematical spaces (Hilbert space) had lived in
the same house for 10 years and still didn't know where the drinking
glasses were kept. But no, he wasn't on statins or anything else. He
was the butt of many jokes.
> Obviously you've not seen statin induced transient global amnesia, or
> recognized it when you did. If you did see it you would probably put it
> down to aging, or some other medical condition.
No, being an expert at evaluation of mental status, it's likely I would
do none of those things. But transient GLOBAL amnesia without trauma,
total brain metabolic deprivation (oxygen, glucose, cerebral pressure
increase) is extremely rare in the absence of the known amnestic drug
(of which statins are not a category), and I don't believe I've ever
seen anything like the odd cases you're describing. But I've never met
a saucer-abduction victim, either. I've had people who swore they'd
seen ghosts (never naked ghosts-- these apparitions are always modest)
and a few people who've had religious visions of one sort or another.
There are a lot of people who have very strange mental experiences too
transient to quantify. Some of them are probably having partial
seizures of some kind. Either that, or Jesus really did appear to Saul
of Tarsus on the road to Damascus, and you and I and the Jews and
Muslims are all in big trouble.
> People cover up, cope,
> isolate themselves, don't speak, get fired, move to jobs done at home
> where they are not observed, are ridiculed when recognized as being
> cognitively impaired, but the reason denied, denigrated and ridiculed,
> as you do here.
COMMENT:
We've now moved on from the topic of transient global amnesia, now,
haven't we? Or did I miss the segue.
I attempt (not without an emotional lapse or two) to save my USENET
ridicule for the willfully stupid. And if you're thinking of asking me
how one can tell if somebody is being willfully stupid on the nets,
you'll just end up being self-referentially illustrative. Ridicule is
the appropriate response for people who advance high convoluted and
abstract arguments for their ideas about reality, and are resistant to
all data to the contrary, either ignoring data entirely, or claiming
giant conspiracy, or (at best) adding even more epicycles to their
arguments (see Copernican astronomy and US Iraq policy).
> You see it in front of you everyday. What do *you* put it down to when
> one who had passed entrance exams for law school just prior to using
> statins now is often "barely comprehensible" (your words for me).
COMMENT:
That's rare. You're usually all too comprehensible. Though willfully
stupid, often enough. :) If you were *never* comprehensible, that
would be something else (there are some psychotics on the nets). Also,
if you were comprehensible but always of ploddingly average
intelligence.
You know the many reasons people of known mental ability deviate from
perfect Vulcan assessment of the world, as well as I do. You're being
willfully stupid. I don't think I really need to list them, except that
there are about a hundred causes that have nothing to do with statin
drugs. The extreme of many of these processes we call "mental illness."
But you don't need to be mentally ill to have a fixed delusion. We all
have a few. You've claimed to see wide variations in the quality of my
own writing, and you're probably right. But I'm not presently taking a
statin, or anything else of consequence. Rather, I'm just another human
being. If I were to be sick and tired and angry and poor and Canadian
(the last straw), I'm sure I'd be even *more* of a human being. But if
so, I wouldn't blame it on Lipitor.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: CABG Alzhelimer's Study
Date: 30 Aug 2005 19:56:08 -0700
Message-ID: <1125456968.637207.131900@o13g2000cwo.googlegroups.com>
zee wrote:
> What's this schtick with Golomb? She's not Canadian as far as I know.
> But you're "not so sure" about me...finally. I've gotten through to
> you. I__can't__read. Neither can most of those who have had my
> experience on statins.
The "schtick" with Golomb is she appears to have a preconceived agenda,
and it seems to be not only mostly data-free, but also data-proof. I
just gave several examples of how she's doing some very fancy footwork
to avoid the easiest and most obvious interpretations of the available
evidence. That's not good science.
Don't make too much of my remarks about Canada. It has a national
character which differs somewhat from its individual people, in
somewhat the same way the US does. And Canada is of course not
homogenous, but differs almost as much politically from Alberta vs. the
Canadian East, as the US does from Utah to Massachusetts, and probably
for much the same reasons. I know this. Some of my best friends are
Canadians. I generally find Canadians delightful. But some of their
ideas about medical care are willfully stupid. And that goes for US
idea also. Somewhere both systems need to meet in the middle, and keep
the best feature of both while tossing out the stupidities.
> Subtle changes are subtle changes. You might miss them on a
> > phone interview, but that doesn't get you out of the conclusion that
> > any changes (if any) are at worst, *subtle.*
>
> Subtle in one. Not so subtle in the next. Do I misunderstand how
> studies are done? Is everyone performing the same? Lay it out Oh
> Disengenuous One.
COMMENT:
Every study is different. But not one study which has looked at the
mental status in a placebo-controlled statin study has managed to find
anything but subtle changes at the group level, or else no changes at
all (the finding in all the the very largest studies which have looked
at mental status). I know of no exceptions, study-wise. At the
individual level are case reports by very bad mental effects, and one
never knows what to make of case reports. I feel about them the same
way as I do about case reports of children who develop-- say--- ADD in
response to food colorings or something. I don't disbelieve them, but
they go in the "weird reactions" file. You don't base your general
practice on them, any more than you quit giving penicillin because of
the occasional allergy.
> > > Crippled with global amnesia...did you think we would have an episode
> > > on the phone to demonstrate for you? It is "transient". Not often
> > > observed, but let me tell you, misunderstood by our physicians and
> > > ourselves.
> >
> > COMMENT:
> > Umm, it's transient and you don't remember even having HAD it? So can't
> > *report* it, when asked?
>
> Not if I don't know what it WAS. Not if I am afraid I may be suffering
> from Alzheimer's, or want desperately not to terrify my family, or want
> to keep my job, or hope *whatever* it was never happens again; or that
> I can hang on until I can't cover up anymore and everyone notices I'm
> lost.
>
> All reasons I have heard others express.
COMMENT:
Always possible, but I'm afraid tha burden of proof here is going to
have to be on claimants. Same as for people with crop circles and so
on.
> What if, when they stop the statin, the aging side effect thing goes
> away (this could be something you should look into for LEF) and then
> when they rechallenge, the aging thing comes back?
COMMENT
Well, I'd be interested in that. I had a patient who thought statins
made his hair grayer, and it got better (over 6 months of course) when
he stopped. I know this has never been looked for, so how would anybody
know? Maybe he was right. But these observations are INPUTS to good
controlled and measured studies (I just wish it wasn't Golomb doing the
big AE one). They aren't things to go around warning people about, on
the basis of stories, which you and the patient-advocate group tell.
That way lies silcone breast implant and aspartame and fluoride
psychosis. Remember, I read the nets and have to listen to tale of how
cow-milk drinking and mercury fillings ruined people's lives. You know,
1 person in 100 is schizophrenic, and a good fraction of these are the
paranoid sort. And some of them have computers and can type. Not all of
them advocate tinfoil helmets. Some of them are sure that we're being
ruined by processed food and iron overload and whatever.
> name dropping...trivializing
COMMENT:
Storytelling in response to storytelling.
> trivializing ... name dropping
COMMENT:
Using examples from history. The "trivializing" only looks like
trivializing to you, because you're being narcissistic and because I
refuse to change my view of the world, which is presently based on my
own experience with hundreds of statin patients, and my careful reading
of studies based on many tens of thousands of them, **on the basis of**
some case-reports by a few people who claim, more often than not, to be
brain-damaged and judgement-impaired. You realize how wacky that is,
don't you? This is a self-defeating argument if ever there was one.
> I can't focus or concentrate. I freely admit it. I have had some kind
> of statin induced brain injury. WARNING!! WARNING!!
COMMENT:
That's the problem. Perhaps you ARE brain-injured in some odd way, or
you'd have the self-insight to see the problem. But most people I meet
who want the world to change to accomodate them, are not brain-injured.
Not in any obvious way. They just have some kind of personality
disorder. Medical science doesn't really know what's wrong with them.
> I'm not a stat. I'm here and real and won't let *you* do what you are
> trying to do without speaking up and saying "it happened to me."
COMMENT:
*Something* happened to you, apparently. The problem is episemological.
How do you *know* what did it? Did you undergo a series of
placebo-controlled tolerance tests, like the ADD kids with the food
colorings? That CAN be done, you know. The woods are full of people
who believed in odd allergies, who got blown out of the water when
tested in the scientific way. Did you rule out strokes in the
non-dominant hemisphere from your sky-high lipids? Have a PET scan?
Have your hormones evaluated? Try an SSRI? See a shrink? If you're
cognatively impaired, it's at some level where it's going be very tough
to get at, even if you lived in the US.
> And for many people who are experiencing statin adverse effects and
> read this, that is all they need to hear.
COMMENT
It may be more than they need to hear. People tend to have the
side-effects they expect to have, which is why mental side effects are
more common in placebo groups in tests of psych drugs, and GI side
effects are more common in placebo groups in tests of NSAIDS. I made
that point, but maybe you missed the implications. It was: do be
careful what seeds you plant. The drug somebody *doesn't* take due to
some self-induced hysteria about its possible side effects, may KILL
them by virtue of its absense. Total mortality WAS down in diabetic
women and women with arterial disease, taking Zocor in the CHS study.
So be sure and tell your "audience" that their lives are at stake here.
> > I attempt (not without an emotional lapse or two) to save my USENET
> > ridicule for the willfully stupid. And if you're thinking of asking me
> > how one can tell if somebody is being willfully stupid on the nets,
> > you'll just end up being self-referentially illustrative. Ridicule is
> > the appropriate response for people who advance high convoluted and
> > abstract arguments for their ideas about reality, and are resistant to
> > all data to the contrary, either ignoring data entirely, or claiming
> > giant conspiracy, or (at best) adding even more epicycles to their
> > arguments (see Copernican astronomy and US Iraq policy).
>
>
> This is just laughable coming from one who continually advances high
> convuluted and abstract arguments.
COMMENT:
But not data-free or data-proof ones, I hope. And if I do, you can take
them as entertainment. I wouldn't ask you to risk your life on them.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: CABG Alzhelimer's Study
Date: 30 Aug 2005 20:33:50 -0700
Message-ID: <1125459230.510053.219730@z14g2000cwz.googlegroups.com>
Sharon Hope wrote:
> Changing "the problem" to what you want to pontificate on does not solve
> "the problem" of my husband's health.
Deciding you know the answer to what caused your husband's health
problems, is not going to help you solve them. Especially if you're
wrong. There are, unfortunately, no criteria for statin-caused brain
injury. No diagnostic tests. No way to formally make the diagnosis. But
perhaps you can help collect the initial data needed for such things in
the future. Meanwhile, you need to rule out known psych and neuro
problems.
> Why not solve that, then maybe I will have the time to read your
> philosophical pontification. Right now there is a real-life, real-pain,
> real-disability, real-life-altering PROBLEM to be solved.
Then, I suggest you have at it. Have you run him through the UCLA
neuropsychiatric diagnostic team? I see Andy Leuchter and Gary Small,
who I trained with, are still there. Andy is particularly compassionate
and knowledgable. And UCLA has some of the finest brain imaging
equipment you can find.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: CABG Alzhelimer's Study
Date: 1 Sep 2005 14:41:56 -0700
Message-ID: <1125610916.935222.124360@g43g2000cwa.googlegroups.com>
Sharon Hope wrote:
> Statin sensitive NP tests were published months ago. You are out of date.
Don't make me laugh. Statin-sensitive is not statin-specific, which is
what a diagnositic test needs to be. The effects of pregnancy can be
seen on many a blood test, but none of them would make good tests for
pregnancy, or are used in such a manner.
> Not to mention unprofessional.
LOL. Ours is not a professional relationship, and does not require
behavior appropriate for one, from either of us. In case you hadn't
noticed, you are not my patient; I am not your doctor. You have no
doubt been thinking that this state gives you the opportunity to say
things to me that you wouldn't or couldn't say to your actual
doctor(s), which they badly need to hear from SOMEBODY. Fine.
But that works both ways.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Cognitive problems with simvastatin?
Date: 1 Sep 2005 20:19:03 -0700
Message-ID: <1125631143.331283.95020@f14g2000cwb.googlegroups.com>
Sharon Hope wrote:
> Ever heard of HIPPA ?
Doesn't apply if patient consents to information release. Do we not
know about Ronald Reagan's colon and Jimmy Carter's hemmorrhoids?
> Generalities are fine in a ng. Specifics of personal medical records are
> not appropriate here.
They are if you insist they be used to change prescribing practices all
around the world! I
> Yours, for example, is certainly not an opinion I
> would seek. I have already stated the caliber of physicians we see.
We've heard your hearsay about it, yes. That's it. You did say all this
had be written up somewhere? But you forgot to give the citations. I'd
be interested, because I cannot find any case reports of permanent
statin-induced brain damage. Not even suspected ones.
You're presently trying getting the "word out" on a medical case on
which you're keeping the medical details secret.
Sorry, but that's a foul. You continue to do it, and we'll continue to
call you on it.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Cognitive problems with simvastatin?
Date: 2 Sep 2005 12:23:50 -0700
Message-ID: <1125689030.627728.30980@g44g2000cwa.googlegroups.com>
fresh~horses@despammed.com wrote:
> Gosh! Medical details kept secret? Naw couldn't be...
>
> Baycol, Lipitor, Vioxx, Paxil...
>
> Naw. Couldn't be...
COMMENT:
Every invesigator has the right to have first crack as his or her own
data, before releasing it. This avoids shoot-from-the-hip bad analysis.
But so long as the data IS eventually released, there's no problem with
the scientific process.
Please note the essential fact that all the bad info on the drugs you
listed above was released BY the scientists and drug companies
involved. None of that data as a result of being "blown" or leaked by
Woodward and Bernstein and some kind of pharma Deep Throat. We HAVE
that information, *because* they made it public. You can use that list
above *precisely* because it is NOT secret.
I don't think Sharon's asking for more time to do her statistics. I
think she's just saying "Bugger off; I want the world to believe this,
based on my stories, and as for hard evidence, it exists but the public
will ever see it. Just take my personal word for it."
And my answer to that, is "No, if that's your supporting documentation
for your claims, then YOU bugger off." It's not going to fly. That's
not the way we do things in science.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Cognitive problems with simvastatin?
Date: 2 Sep 2005 14:28:38 -0700
Message-ID: <1125696518.116401.110990@g14g2000cwa.googlegroups.com>
fresh~horses@despammed.com wrote:
> Sharon can speak for herself.
>
> Here's my answer: Get a grip.
>
> I'll paraphrase: this here's usenet. Just because you demand an answer
> doesn't entitle you to one.
> {Steve Harris: usenet circa 1997}
COMMENT:
Sure enough. But burden of proof is ever with the claimant. If you
don't have, or won't provide, the evidence to back your medical claim,
THEN you're going to get the horselaugh. That applies to everybody
here, quite democratically. And yes, nobody MAKES you provide the
backup evidence. You can have take the horselaugh instead, if you want.
Free world.
SBH
(And by the way, it wasn't me that asssumed Mike Hope had been written
up in medical journals. Sharon volunteered that fact, in the course of
her argument. But he must be written up in double-secret journals, I
guess, since citations have we none.)
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Cognitive problems with simvastatin?
Date: 3 Sep 2005 17:46:41 -0700
Message-ID: <1125794801.007801.174470@g49g2000cwa.googlegroups.com>
fresh~horses@despammed.com wrote:
> Zee posted an a letter that Dr. Torgovnik chose to have published in
> the Annals of Internal Medicine; published research de facto, using
> himself as patient. That means, he held permission and gave permission,
> in two different ways.
>
> Your analogy does not follow for Michael Hope. Michael Hope would have
> to give permission for this to happen. He is still the owner of his
> medical information.
COMMENT:
Of course, that goes without saying. Don't be obtuse. When we noted
that HIPAA did not apply when the patient has given permission, we were
al fully aware that Mike is the patient. Duh.
So let him give permission. Otherwise let his wife zip it.
[BTW-- Come to think of it, I'm not even sure HIPAA applies even if
Sharon didn't get Mike's permission. HIPAA's a bunch of fed guidelines
to hospitals and insurance companies about what security they have to
have. It doesn't apply to what your spouse obtains from you personally,
then posts to the web. I doubt Mike would realistically have any legal
recourse but to file for divorce. Certainly the Feds aren't involved at
this level, once the info has left the institution.]
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Lipitor not better than rivals. doesn't prolong life for diabetics
Date: 4 Sep 2005 16:07:34 -0700
Message-ID: <1125875254.533549.140170@o13g2000cwo.googlegroups.com>
Sharon Hope wrote:
> Note in particular:
>
> "Lipitor, the world's best-selling drug, is no more effective than
> similar drugs and in some cases has WORSE SIDE EFFECTS, according to a
> study by an independent German institute."
>
> "It noted that some studies on Lipitor HAD TO BE STOPPED because it had
> MORE SIDE EFFECTS compared with Zocor."
>
>
> <fresh~horses@despammed.com> wrote in message
> news:1125873013.446178.310880@f14g2000cwb.googlegroups.com...
> >
> > AP
> > Study: Lipitor No Better Than Rivals
> > Sunday September 4, 4:53 pm ET
> > Cardiovascular Treatment Lipitor, World's Best-Selling Drug, No Better
> > Than Rivals, Study Says
> >
> > DUESSELDORF, Germany (AP) -- Pfizer Inc.'s cardiovascular treatment
> > Lipitor, the world's best-selling drug, is no more effective than
> > similar drugs and in some cases has worse side effects, according to a
> > study by an independent German institute.
> >
> > The results come from a survey of previous studies worldwide, rather
> > than new clinical tests on patients. It was released Saturday by
> > Institut fuer Qualitaet und Wirtschaftslichkeit im Gesundheitswesen.
> >
> > IQWiG is an independent institution that studies value-for-money in
> > health care, set up at the instigation of the German government.
> >
> > The study follows a controversy in Germany about the pricing of Lipitor
> > and other statin drugs, which aim to reduce cholesterol levels.
> >
> > According to IQWiG, life-prolonging results for patients suffering from
> > chronic coronary heart disease was seen with Merck & Co.'s Zocor and
> > Bristol-Myers Squibb Co.'s Pravastin -- but not with Lipitor.
> > In acute diseases, there weren't enough data to prove that any of the
> > group -- Lipitor, Zocor or Pravastin -- was better than the other.
> >
> > With diabetes mellitus, only Merck's Zocor was shown to prolong life.
COMMENT:
Please note my many notes to this group on why I only prescribe the
three oldest statins: mevastatin/Mevacor, simvastain/Zocor, and
pravastatin/Pravachol. They are the ones with the giant trials. They
deserve your patronage and respect for funding them. We don't know
enough about the newer ones, and we were running the risk of getting
another Baycol, or just such results as you see above.
The problem is insurance companies and HMOs have been pushing Lipitor
because it gives more LDL lowering per buck (and they sometimes also
offer Mevacor). So the two statins we know most about, Zocor and
Pravachol (in that order), get short shrift because people think
they're being ripped off, and don't realize (or don't care) that
they're paying for information as well as the drug (which has a very
low marginal cost).
The old problem: people are information-socialists. They think
information should be FREE! They rebel if charged for it, and think
they're being ripped off. And then, when they inevitably suffer the
consequences of acting on poor information because they were too cheap
to obtain it, they believe themselves victims of an evil plot. Well,
the evil plot was that they got what they paid for, instead of what
they thought was due them free, out of the goodness and kindness of the
universe (or the government).
You've heard me say "wait" on Lipitor. You've heard me denigrate
Crestor. As Wilde said, "the plain and simple truth" is rarely plain
and never simple. In this case, statins are not good, and statins are
not bad. Rather the universe is complex, and some statins are better
than others. Also, there is rarely such a thing as a bad drug. But
there are certainly BAD combinations of PARICULAR PEOPLE AND PARICULAR
DRUGS.
But now we generalize: that's true of all drugs. Even the ones the
Narcs like to jail people for using. Fundamentalist minds, which are
simply incapable of seeing anything (drug or human) in any other terms
than black and white, cannot come to grips with the grayness of
reality.
Hopefully, by means discussions such as these, some of the rest of us
can do a little better.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Lipitor not better than rivals. doesn't prolong life for diabetics
Date: 5 Sep 2005 16:01:18 -0700
Message-ID: <1125961278.339645.109130@g49g2000cwa.googlegroups.com>
fresh~horses@despammed.com wrote:
> "Also, there is rarely such a thing as a bad drug. But there are
> certainly BAD combinations of PAR{T}ICULAR PEOPLE AND PAR{T}ICULAR
> DRUGS. But now we generalize: that's true of all drugs. Even the ones
> the Narcs like to jail people for using."
>
> Kudos. Spoken like the pure chemist I suspect you are.
>
> Zee
COMMENT:
Though I have a degree in chemistry and am presently slaving over a
chemical patent, what I spend most time doing is experimental
physiology. My next paper (manuscript just arrived and undergoing final
editing now) will treat successful use of a new preparation of general
anesthetic in horses (veterinary medicine and pharmacology). My
previous paper and abstracts covered the topic of induced hypothermia
in dogs, as a model of post-resuscitation encephalopathy prevention
(resuscitation physiology). Coming up next is a case report of a
radical and successful treatment of sinonasal/brain cancer in 2 humans,
using proton radiation and intra-arterial chemo (RADPLAT+protons). I'm
the first to have done that, back in 2000 (nobody's done it since--
it's horrendously complicated and only a few places have medical
synchrotrons). That's experimental medicine: oncology. Somewhere I have
to write up 11 trials of absorption performance of coenzyme Q10
preparations in humans, done over the last year--- more of a
nutritional topic. So I'm not a "pure" anything.
I am proud to be a scientist. In any case, the divisions within science
are artificial.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Lovastatin
Date: 4 Sep 2005 16:29:45 -0700
Message-ID: <1125876585.721731.43360@g43g2000cwa.googlegroups.com>
ahpol961@gmail.com wrote:
> I have gone from Lipitor to Lovastatin for lowering my
> chlorestral. (Not sure of spelling)
> I am trying to keep my memory intact. Does anyone know
> if this was a better choice, or not.
> I am 84 yrs old and I have to help myself as much as I can.
> Ann
What does your doctor say? The statin what stays out of your brain the
best is pravastatin (Pravachol). But lovastain (Mevacor, Altacor) is
probably a better choice than Lipitor.
That said, Pravachol did NOT help elderly people in the the PROSPER
trial. The only statin proven to do that is Zocor/simvastatin. And even
that hasn't been proven for the elderly who merely have high
cholesterol but nothing else wrong.
Talk to your doc. Again, the statin we know most about, and also the
only one proven to extend life in the elderly (with vascular disease or
diabetes), is Zocor.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Selenoprotein synthesis:includes discussion of statin side effects
Date: 4 Sep 2005 17:29:37 -0700
Message-ID: <1125880177.142123.73920@g14g2000cwa.googlegroups.com>
Sharon Hope wrote:
> Thyroid. 2005 Aug;15(8):769-75.
>
> Selenoprotein synthesis: a unique translational mechanism used by a diverse
> family of proteins.
>
> Hoffmann PR, Berry MJ.
>
> Department of Cell and Molecular Biology, University of Hawaii at Manoa,
> Honolulu, Hawaii.
>
> The purpose of this review is to provide an overview of the unique mechanism
> by which mammalian selenoprotein synthesis occurs. Selenoprotein synthesis
> requires translational recoding of the UGA codon from a stop signal to a
> selenocysteine insertion signal (SECIS). Dedicated factors directly involved
> in this translation process include specific secondary structure in the mRNA
> (SECIS), a unique tRNA (Sec-tRNA(Sec)), an RNA binding protein (SBP2), and a
> specialized elongation factor (EFsec). Regulation of this process is
> discussed along with physiologic and clinical issues regarding selenoprotein
> synthesis, including the side effects associated with statin drugs.
>
> PMID: 16131320 [PubMed - in process]
COMMENT:
For the layman, the tie-in here is that the de-iodinase that converts
T4 to T3 (the active thyroid hormone) is a selenoprotein with selenium
at the active site. All the readers of _Thyroid_ know this, but the
general reader may not.
There is some suggestion that high doses of statins may interfere with
selenoprotein sythesis in a general manner. This is especially
important in that Selenoprotein N loss causes a congenital myopathy
which looks a lot like statin myopathy. There is also a Se-depedant
antioxidant enzyme (glutathione peroxidase) which you'd like to have in
high levels in your body, since it regenerates oxidized glutathion to
the reduced form which used by the body to repair all kinds of
oxidative damage.
As in all drug effects, all this stuff is both dose dependent, and
subject dependent. I well remember when the thyroid effects from
amiodarone made it a drug used with fear and trepidation by
cardiologists, as a last resort. Today it's used widely and almost
routinely. Never let biochemistry scare you--- it does not substitute
for clinical trial actual findings. Watch your PERSONAL clinical
results. Do drug holidays on patients who don't look or feel well--
they may represent sensitive cases. And in all cases: treat patients
first, lab numbers second.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Selenoprotein synthesis:includes discussion of statin side effects
Date: 4 Sep 2005 18:51:29 -0700
Message-ID: <1125885089.451614.53580@f14g2000cwb.googlegroups.com>
zwalanga@yahoo.com wrote:
> I well remember when the thyroid effects from
> > amiodarone made it a drug used with fear and trepidation by
> > cardiologists, as a last resort. Today it's used widely and almost
> > routinely.
>
>
>
> WARNING STALLED AS HEART PILL KILLS
>
> Patient advisory promised by U.S. agency last year
>
> November 26, 2004
>
> BY ALISON YOUNG
> FREE PRESS WASHINGTON STAFF
>
> WASHINGTON -- A highly toxic heart drug continues to be prescribed to
> millions of patients nationwide without the detailed consumer warnings
> promised by the U.S. Food and Drug Administration more than a year ago.
Yep. So? The stuff is prescribed for heart dysrhythmias which are far
more dangerous than the drug is.
"Detailed consumer warnings" are not the answer. Patients need to be
warned about the cough and the vision problems specifically and
directly, and to have blood tests. A bottle label like this would do:
"Chronic cough after starting Cordarone may be a sign of lung damage,
which can be fatal if drug is continued. Tell your doctor if you think
you have new breathing problems. Visual disturbances from this drug may
be a sign of problems which can lead to blindness, if not treated. See
your doctor for regular liver and thyroid blood tests while taking
Cordarone.
That's it. For a nation that reads on a grade 6 level, most package
inserts as now written, should be *inserted* up the behinds of FDA and
pharmaceutical corporate lawyers. Folded first so they have sharp
corners. Cardiologists know about the blood tests, and also should be
warning patients about the lung and vision stuff, but it's nice to have
printed backup for everything a doctor tells you. I never let a patient
leave a consultation without a written outline of what I've told him. I
write it myself, while I'm talking. Bullet-style, like a Powerpoint
presentation. I print normally, so I'm not illegible (put my spelling
errors down to hurry...). I think it's a good habit for all doctors to
get into, and most do it. If your handwriting is bad, you can always
type on a laptop, UK doc style, and print it out. That kills two birds
with one stone if you're also a bad speller.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Selenoprotein synthesis:includes discussion of statin side effects
Date: 4 Sep 2005 20:54:24 -0700
Message-ID: <1125892464.597899.144180@g47g2000cwa.googlegroups.com>
zwalanga@yahoo.com wrote:
> >I never let a patient
> > leave a consultation without a written outline of what I've told him. I
> > write it myself, while I'm talking. Bullet-style, like a Powerpoint
> > presentation. I print normally, so I'm not illegible (put my spelling
> > errors down to hurry...). I think it's a good habit for all doctors to
> > get into, and most do it. If your handwriting is bad, you can always
> > type on a laptop, UK doc style, and print it out. That kills two birds
> > with one stone if you're also a bad speller.
> >
> > SBH
>
>
>
> Commendable. Truly. More physicians should do that. How would you
> respond to a patient request to bring in a third person; or a
> taperecorder? Not all the time you understand, but for worrisome
> consults, perhaps.
The third person is almost standard for geriatrics. It's usually the
patient's daughter or daughter-in-law.
Had a recorder brought once. No problem. He was a rich guy who had his
secretary transcribe it all, though, and wanted me to edit it the next
time. This can get mighty old.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Selenoprotein synthesis:includes discussion of statin side effects
Date: 4 Sep 2005 19:34:50 -0700
Message-ID: <1125887690.510043.277660@f14g2000cwb.googlegroups.com>
Sharon Hope wrote:
> Be aware that low thyroid is associated with breast cancer.
How so? I found one study in which women diagnosed with breast cancer
were half as likely to be taking thyroid hormones because of a previous
diagnosis of hypothyroidism. In otherwords, women who'd been diagnosed
as hypothyroid and given hormones had half the breast cancer risk. But
this needs to be checked prospectively.
There does seem to be association of breast cancer and thyroid
autoimmune syndromes, including thyroid enlargement and anti-thryoid
antibodies. But the direction of cause and effect is not clear.
Probably both are caused by some general derangement of body immunity.
As for women with active breast cancer who are ill, any disease can
give you a "euthryoid sick" syndrome, particularly those that make you
lose weight. Levels of T3 go down due to reduced liver conversion of T4
to T3. Most endocrinologists don't regard it as true hypothyroidism.
But there, the breast cancer causes low T3, not the other way around.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: 500,000 more Canadians should take statins
Date: 23 Sep 2005 19:29:30 -0700
Message-ID: <1127528970.262221.65020@g14g2000cwa.googlegroups.com>
fresh~horses wrote:
> From the Toronto Star (09/21/05)
>
> Selling sickness to the masses
>
> Vast numbers of low-risk people are prescribed
> medication that has little effect, says Alan Cassels
>
> <http://www.thestar.com/NASApp/cs/ContentServer?pagename=thestar/Layout/
> Article_Type1&c=Article&cid=1127211479351&call_pageid=968256290204&col=9
> 68350116795>
<snip>
> Those at "high risk" may reduce the threat of having a
> heart attack over
> 10 years by about 5 per cent or 6 per cent by taking a
> statin every day.
COMMENT:
That's just plain wrong, if you look at the best evidence available.
The largest controlled statin study ever done (HPS), funded mostly by
the British health service, found typical reductions of 30% over 5
years in vascular events in high risk groups. For example, if you've
had one heart attack, your chance of another in 5 years is about 30%.
With a statin, that drops to 20%. So 1 heart attack in 10 is prevented,
over 5 years.
The HPS study found that women as well as men benefited from
simvastatin 40 mg, and also people older than 70, and even people with
cholesterol under 200 mg/dl, if they were also diabetic. As compared
double blind with placebo. Total mortality in the statin group was also
decreased substantially.
> ------------------------------------------------------------------------
> --------
> Alan Cassels is the co-author with Ray Moynihan of
> Selling Sickness: How
> the World's Largest Pharmaceutical Companies are
> Turning us all into
> Patients.
He might start with honest statistics.
Since the aging process is destined to make all of us eventually into
frail, knarled, stiff and trembling versions of ourselves (at best),
waiting for some medical event to finish us off, it's rather inevitable
that as understanding of biology increases, that anybody who isn't
happy with THAT prospect will eventually become a "patient," in an
attempt to slow up the process, or stave it off a few more years. It's
not a dirty word. It merely means you don't like the status quo.
Some people will accept the status quo, and refuse all medical
intervention. That's fine. Just don't lie to yourselves. Absolute
mortality reduction was 1.8% for this study over 5 years, which is the
same as saying that skipping the drug for 5 years if you have a major
vascular risk is about like deciding to do something as likely to kill
you as (say) taking a ride on the space shuttle (2/114 = 1.8% loss rate
there also). It's not huge. But it's not small, either. If you like to
live dangerously, have at it.
As for me, the older I get, the better Zocor looks. I might ride the
space shuttle, too. For every decision, there are risks and benefits.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: 500,000 more Canadians should take statins
Date: 23 Sep 2005 22:20:48 -0700
Message-ID: <1127539248.464179.182230@f14g2000cwb.googlegroups.com>
fresh~horses@despammed.com wrote:
> > The HPS study found that women as well as men benefited from
> > simvastatin 40 mg, and also people older than 70, and even people with
> > cholesterol under 200 mg/dl, if they were also diabetic. As compared
> > double blind with placebo. Total mortality in the statin group was also
> > decreased substantially.
>
>
> It was still only for **SECONDARY** prevention. *You* might start with
> honesty.
COMMENT:
"Honesty"?? Okay, honestly, statins reduce stroke and MI by only 16%
(half has much) in primary prevention trials (ie, no stroke or MI yet).
As you'd expect, it's not as much, but it's still more than the article
you quote. And total mortality by 5%, which is not quite significant
(0.88-1.02 are the 95% confidence limits for the 5 largest
mostly-primary prevention trials). And honestly, that is mainly because
mostly primary prevention trials like ASCOT were stopped short for
ethical reasons at 3.3 years (planned for 5) when MI and stroke data
reached significance. The mortality risk ratio in that trial was 0.87
confidence limits 0.71 - 1.05. Gunna bet your life that's not real?
Honestly you can't fault statin drugs for not reducing mortality when
the best primary trials were designed to be stopped before a very clear
trend breached significance.
> You'd be amazed at the number of people who, rather than have their
> stance on healthcare begin and end with pharma, make weight control,
> exercising hard and being at best BMI their first line of defense
> against frailty and disintegration.
You think I don't know the stats on BMI's? Hint-- they're going up
everywhere. What makes you think I'd be "amazed"? Show me the primary
prevention mortality rates for BMI reduction, please. Randomized weight
loss program please, since I will pay no attention to studies whose
conclusions are that healthy people tend to stay healthy. Everybody
knows that already.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: 500,000 more Canadians should take statins
Date: 24 Sep 2005 20:44:44 -0700
Message-ID: <1127619884.334780.47190@z14g2000cwz.googlegroups.com>
Jim Chinnis wrote:
> >The largest controlled statin study ever done (HPS), funded mostly by
> >the British health service, found typical reductions of 30% over 5
> >years in vascular events in high risk groups. For example, if you've
> >had one heart attack, your chance of another in 5 years is about 30%.
> >With a statin, that drops to 20%. So 1 heart attack in 10 is prevented,
> >over 5 years.
>
> 1 in 3, not 1 in 10. I think you meant, "1 heart attack per 10 people
> treated."
> --
> Jim Chinnis Warrenton, Virginia, USA
Wups. Yes, indeed.
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: 500,000 more Canadians should take statins
Date: 26 Sep 2005 02:32:12 -0700
Message-ID: <1127727132.633266.101590@o13g2000cwo.googlegroups.com>
fresh~horses@despammed.com wrote:
> > You think I don't know the stats on BMI's? Hint-- they're going up
> > everywhere. What makes you think I'd be "amazed"? Show me the primary
> > prevention mortality rates for BMI reduction, please. Randomized weight
> > loss program please, since I will pay no attention to studies whose
> > conclusions are that healthy people tend to stay healthy. Everybody
> > knows that already.
> >
> > SBH
>
>
> Why so picky all of a sudden? You pay attention to studies which show
> statins are only better than nothing.
When they randomize people to statins or exercise, I'll be glad to look
at that. But let me warn you, if you think a high drop-out rate in the
run-in phase invalidates an intention-to-treat study, you've pretty
much shot yourself in the foot on all the aerobic exercise stuff. You
think the 1/3 dropout rate of HPS was bad! Oh, boy.
Nor are there any good PROSPECTIVE studies to show that exercise
decreases mortality, except as secondary treatment after MI. Sound
familiar? And nothing RCT propective on exercise and primary mortality
prevention in women at all. Sound familiar?
I'm just asking you to apply same level of skepticism to all things.
Myself, I think that fact that the MI rate drops 30% and mortality 10%
in the secondary statin trials, and the rates in primary are 15% and 5%
(exactly in synch) is just as expected. If the mortality at the last
didn't quite make significance, it's because it wouldn't be expected
to, at those MI prevention rates.
I suspect exercise is the same story. If it works in secondary
prevention you'd have to be postulating some pretty seriously bad side
effects to suggest it doesn't work in primary prevention. Particularly
if the odds are running the direction they're supposed to. But it's all
inference.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: 500,000 more Canadians should take statins
Date: 26 Sep 2005 02:59:36 -0700
Message-ID: <1127728776.200460.141460@g44g2000cwa.googlegroups.com>
fresh~horses@despammed.com wrote:
> BMI. Who cares?
>
> What did you do today...eh?
>
> What did you do today to get into your heart rate?
>
> Can you walk the talk about health and prevention? Or do you just know
> how to quote stats?
COMMENT:
Oh, I usually walk or swim. On the road, as last week, I get exercise
where I can. Worked as a volunteer "roadie" for a tech conference at
Stanford, huffing and puffing and carrying around Klieg lights and
junk. Later walking again around Steinbeck country and Cannery Row in
Monterey. Noting the disneyfication, which is inevitable. (History
repeats, first as tragedy, then as farce, says Marx, but doesn't add
that the third time is as theme park). Climbed the 10 steps to the
landing at Doc Ricketts' lab, a pilgrimage I hadn't made in a decade.
Walking up to the intersection at Drake and Wave where Doc was killed
by the train, and finding to my shock an effigy of Doc himself there.
There had previously been no marker at all. I'd actually suggested one
in a visitor's book a decade ago, and it's possible I even had
something do with this (along with many another tourist).
Driving home, found myself driving through Paso Robles and past Chalom,
and behold, there's the tree with the weird Japanese memorial to James
Dean, killed in a car accident there, still out in the middle of
nowhere, 50 years ago next week. People leave coins there now, and this
almost must have started since I last saw the place a decade ago.
There's even a ghostly connection, as Dean had starred in the movie
version of Steinbeck's East of Eden.
So it seemed to be my time to walk past places where semi-famous people
had been run over. Felt like a ghost myself, as I usually do when
traveling. Things change. Steinbeck, when he went back to Monterey in
Travels with Charley, felt like a ghost himself, there had been so much
change. And that was in 1960, 45 years ago. I think Doc and Steinbeck
would have liked the Aquarium that now fills the corner building of
cannery row. But Doc hated to get his head wet, and all his life he
never saw what he thought of as "tide pool" invertebrates as they
really live, as you see them in such a aquarium, or in scuba. I think
somebody had ONE dive mask in the Sea of Cortez, and nobody used it
much....
Anyway, I do get out.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: 500,000 more Canadians should take statins
Date: 27 Sep 2005 17:28:58 -0700
Message-ID: <1127867338.949651.317650@g14g2000cwa.googlegroups.com>
fresh~horses@despammed.com wrote:
> What dose do you take of which one? And what is your weight and height
> again?
225 lbs = 102 kg as of this AM. Height 6'3" = 190 cm. Again, not
great, but what did you say your own BMI was, again?
Right now, dose of statin is none. I've taken pravachol in the past (a
year ago). Right now (last month), on nothing but 10 grams a day of
fishoil, vitamins (no niacin), and some exercise, I'm running at:
Cholesterol 180 mg/dL total
Triglycerides 134 (149 upper limit at my lab)
HDL 45
LDL 108
Divide by the usual 38.6 factor to get SI molar concentration values.
(The US values are metric, of course--- they're just not SI chemistry)
Glucose 90 mg/dL fasting (divide again by 18 to get SI chemical
values).
These aren't all that fantastic. The relatively low HDL is due my
gender and would be 40 in me without wine and walking. On 20 mg
pravachol I ran at total cholesterol 150, LDL 75, which would in theory
be nearly optimal. So I'm thinking about low dose Zocor. But I'm also
in the middle of CoQ10 trials, so I can't fiddle around with my lipids
experimentally because that screws up the CoQ10 values.
> Really tired of everyone being sold a bill of goods for what *may* have
> some minor efficacy for a 240 lb, 6'3 middle aged man.
I've never been that heavy in my life.
> Give me your lecture on risky California highway driving
> again--completely cancelled out by what you personally do with statins.
Please read essay on taking risks. I said you could ride the shuttle,
or not take your medicine. Up to you.
> Here's an idea: you apply your "taking a drug to see what it feels
> like" method to Lipitor. Start at 10mg daily, and just keep going up
> until it hits you.
>
> Report here.
It's a thought. High doses of Pravachol make me sensitive to cold (an
odd side effect I've never seen anywhere else). Zocor at 20 seems to be
side-effect free. I haven't had any Lipitor around to take, but next
time somebody gives me a bottle of their old stuff, I believe I will.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: 500,000 more Canadians should take statins
Date: 27 Sep 2005 19:27:10 -0700
Message-ID: <1127874430.410705.154810@f14g2000cwb.googlegroups.com>
fresh~horses@despammed.com wrote:
> > Cholesterol 180 mg/dL total
> > Triglycerides 134 (149 upper limit at my lab)
> > HDL 45
> > LDL 108
>
> Steve we have to get your HDL up. Why so low do you think?
Testosterone. It's a pretty average HDL for a man, unless he's lucky to
get one of whose "high HDL genes". Which I didn't.
Castration has been suggested, but I resist. Besides, although that
raises HDL levels it does not seem to decrease cardiovascular risk in
men, for reasons unknown.
There is one study of male castration in humans and life-span.
Controlled as well as they could, they compared survival records of
male mental patients who'd been castrated for genetics/control reasons,
or not (this used to be fairly commonly done-- pretty much as in the
Sound and the Fury), before being released. Castrated males lived
slightly longer in the community, but the difference was only due to
fewer deaths from TB (this was done in an age when TB still killed
people). Thus we infer that TB was somewhat of a social disease.
> > Glucose 90 mg/dL fasting (divide again by 18 to get SI chemical
> > values).
>
> Is that a problem? I don't know those values.
No, numbingly average.
> > These aren't all that fantastic. The relatively low HDL is due my
> > gender and would be 40 in me without wine and walking. On 20 mg
> > pravachol I ran at total cholesterol 150, LDL 75, which would in theory
> > be nearly optimal. So I'm thinking about low dose Zocor. But I'm also
> > in the middle of CoQ10 trials, so I can't fiddle around with my lipids
> > experimentally because that screws up the CoQ10 values.
>
> You're your trial animal.
Have been for years. And everybody else in the lab. And the staff and
volunteers, and the contract accountant and my masseuse, etc, etc. When
people I know see me approach, they reflexively cover their antecubital
fossae.
> > It's a thought. High doses of Pravachol make me sensitive to cold (an
> > odd side effect I've never seen anywhere else). Zocor at 20 seems to be
> > side-effect free. I haven't had any Lipitor around to take, but next
> > time somebody gives me a bottle of their old stuff, I believe I will.
>
> Check the mail.
>
> While I have you to hand; doc I saw today was very skeptical of me
> taking 5 1,000 mg fishoil caps. Added to my diet, that't too much fat
> *for me* he said.
>
> Yes? No?
Nonsense. 5 g = 45 Cal = 3% of your calories. What's this guy aiming
for? You could triple that without harm.
> My cholesterol is still sitting at 9.7; ldl almost 8, tris almost
> non-existent.
>
> I could only do 4 km at my target heart rate today. The Harriers were
> running. I had to stop to admire the scenery.
>
> ; )
>
>
>
> Zee
>
> {old but not dead}
With those horrible numbers (cholesterol 374 LDL 300) would suggest
screening stress-echo or stress nuclear scan. Else you might get to
experience the second before more of the first.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: 500,000 more Canadians should take statins
Date: 28 Sep 2005 00:07:20 -0700
Message-ID: <1127891240.654887.319570@g44g2000cwa.googlegroups.com>
Hawki63@sbcglobal.net wrote:
> haha...Zee doesn't BELIEVE in "uber technology"...
> has never heard of anyone dropping dead after running
Or during. The idée fixe of Fixx: if you CAN run, then it's not
dangerous for you to run. And you'll be immune to heart disease if you
can do a marathon. They found Jim Fixx in the road, with coronaries all
plugged nearly up. Man, that guy could take pain. Having ignored his
cholesterol. I keep his book on running on my shelf to remind myself of
dumb ideas in health.
SBH
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Possible problem lowering triglycierides too much with Lipitor???
Date: Wed, 05 Oct 2005 07:11:15 -0400
Message-ID: <di0cd7$mik$1@reader1.panix.com>
Flycaster wrote:
> I'm 66 yo, 6' tall and weigh 164, play 1.5-3 hours tennis (doubles at
> 3.5 level) 5-7 days/wk, lift weights every other day for 1 hour, with an
> overall muscular and slender build and have always been active and in
> good shape and good health. My mother also was in great shape and
> active, but with high cholesterol (controlled by diet and statin), when
> she suddenly died at 83 (no documented cause) while in apparently good
> health. My last two cholesterol tests (9/03 and 2/05) gave the
> following values respectively:
>
> Total: 205 220
> HDL: 56 65
> LDL: 139 139
> Ratio: 3.7 3.4
> Trigly: 52 82
>
> Although my cholesterol levels have always been in the 200-230 range,
> none of my internists have opted for me to go on statins. They have
> said that my "fat" profiles looked good and precluded the use of
> statins. However, reading about the overall value of statins (I was in
> the pharmaceutical industry for 32 years and know something about how to
> evaluate medical research) and their potential for
> cardio-protectiveness, I recently asked my doctor to place me on a
> statin. My preference was for Lipitor (based on research and the fact
> that it won't cost me anything). The doctor said that he would rather I
> take Prevacol as he felt that Lipitor would lower my triglycerides too
> much.
>
> So, what do you folks feel about my going on a statin and what about
> concerns about lowering my trigly too much?
Pretty much anyone who takes a statin can expect about a 25% relative
decrease in cardiovascular events. However, in absolute terms this
decrease can be very small if the person's baseline risk is small.
More information than just age and lipid profile are needed to calculate
cardiac risk, but most nonsmokers without diabetes or hypertension and
with a relatively low LDL and relatively high HDL (like those above) can
expect a 10-year risk of events of less than 10 percent and probably
less than 5 percent. So in most such people, taking a statin every day
would not be expected to decrease events by more than 1% to 2% over 10
years, and in many people the decrease in events would be even smaller.
I don't know of any particular reason to worry about lowering
triglycerides too much with a statin. The reason for not taking a statin
would be that the benefits are small and there are always potential side
effects. But a reasonable person could choose to take a statin for the
small decrease in cardiovascular events that would be expected.
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Lawsuit questions need for Lipitor
Date: Mon, 10 Oct 2005 22:17:36 -0400
Message-ID: <dif7cj$5qb$1@reader1.panix.com>
fresh~horses wrote:
> MEM, MD wrote:
>
>>You are absolutely mislead on this one-
>>Trial design and funding for Prove It was from Bristol Myers Squibb
>>and BMS only
>>
>>Pfizer provided funding for the reprints of the article that were
>>distributed to doctors.
>>
>>You are correct about the dose comparision. Anyone familiar with the
>>trial would point out that it was a comparison of an aggressive
>>(LDL=70) vs. standard (LDL=100) strategy for lipid lowering post-ACS,
>>NOT a comparison of 80 of lipitor vs. 40 of pravachol.
>
>
> That doesn't make sense. Can you explain that?
>
> The study says it was atorvastatin 80mg vs pravastatin 40. Everyone
> knows two things there right away; one is lipiphillic, the other not;
> and the doses are not equivalent so they aren't going to achieve the
> same result. Nor are they going to have the same side effect profile.
I have to agree, at least in part, with Zee on this one. I don't think
it's fair to assume that everything that happened in PROVE IT is
explained by the difference in LDL lowering. (I also don't think it's
fair to assume that the important difference between the effectiveness
of pravastatin and atorvastatin is related to one being hydrophilic and
the other lipophilic.)
In PROVE IT, benefits were seen with atorvastatin 80 mg in the first 30
days of therapy despite the comparator being another statin. In Phase Z
of the A to Z trial, simvastatin 40 mg (another lipophilic statin)
showed no such early benefit despite the comparator being placebo at
that point in the trial (the trial design is fairly complex, but this
was the comparator in the first month). It's at least possible that
whatever was going on in PROVE IT is not completely explained by LDL
lowering and may have something to do with atorvastatin or the dose used.
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Lawsuit questions need for Lipitor: The ASCOT trial's 2000 women
Date: Wed, 12 Oct 2005 20:24:50 -0400
Message-ID: <dik9h7$rs7$1@reader1.panix.com>
fresh~horses wrote:
> The study refererenced in Roni Rabin's Newsday article at the head of
> this thread ("...2000 women...") is ASCOT, published in Lancet in April
> 2003.
>
> And here is an snippet regarding the lawsuit, with the lawsuit website
> linked below.
>
> David if you want the table for the ASCOT trial I can e-mail it as
> attachment.
>
> MEM do you have a workable address? Anyone wants it say so on group,
> please. Despammed is defunct.
>
>
> Zee
>
> "Although Lipitor has been on the market since 1996,
> it wasn't approved for the prevention of heart attacks
> until 2004. The FDA approved it for this because a
> large study (called the "ASCOT" study) showed that there
> was a reduction in heart attacks overall for the
> approximately 10,000 patients in that study. However, the
> FDA looked at this study as a whole, rather than
> looking at the different types of patients in the study. In
> fact, the women in that study who had no prior history
> of heart disease who took Lipitor actually had 10%
> more heart attacks than the 1,000 women taking a placebo.
> Despite the fact that the FDA approved Lipitor for
> prevention of heart attacks, there is still no reliable
> medical evidence that Lipitor or any other statin is
> effective at preventing heart attacks for women and
> people over 65, who have no history of heart disease."
Okay, it probably should have occurred to me that this was from ASCOT-LLA.
First a philosophical comment about looking at subgroup analyses: they
are usually a bad idea. This applies both in negative studies where
pharmaceutical companies try to find a subgroup the drug worked in, and
positive studies where doubters try to find a subgroup the drug failed in.
In general, a therapy that works in one group has simlar relative
effects in all groups. There are exceptions, but this should be the
default expectation. If I show you a study demonstrating that statins
work in people, and you are short, left-handed, and have brown hair,
it's not generally reasonable to expect that I prove to you that the
study also showed benefit in short, left-handed, brunettes. In the
absence of strong evidence to the contrary, the relative benefit should
be assumed to be the same as in everyone else. By chance alone, when we
start performing subset analyses we will find groups where a proven
treatment appears not to work and where a useless treatment appears to work.
The default assumption, in the absence of strong evidence to the
contrary, should be that statins (and blood pressure medicines, and
antibiotics, and vitamins) have the same relative effects in men and
women. Note, by the way, that this does not apply to differences in
absolute benefit -- women, on average, are at lower risk for coronary
heart disease than men, and so, on average, will get less absolute
benefit from statins than men. But we should expect that women have the
same relative benefit and that a woman who happened to be at baseline
high risk would have the same absolute benefit as a man with the same
baseline high risk.
This should even be the default assumption when a subgroup analysis
appears to show a statistically different effect in one subgroup from
another -- the likelihood of this being due to chance remains high if
the study performed lots of subgroup analyses. However, this was not the
case in ASCOT. ASCOT found no statistically significant difference in
the effect of statins in men and women and so looking at the individual
subgroups is particularly suspect.
Second, ASCOT actually provided almost no data at all on the effects of
statins in women. The comment quoted above about a 10% increase in
events in women is just the sort of disingenous language that one might
expect from a pharmaceutical company trashing a competitor's product or
from someone with a stake in the outcome ignoring the actual evidence
(not that one could ever imagine a litigator doing such a thing).
There were thirty-six primary outcome events in women in ASCOT --
THIRTY-SIX! Nineteen occurred in women taking atorvastatin and 17 in
women taking placebo. Those two events out of 17 represent the 10%
increase the article is apparently referring to. To say that this was
not statistically significant and that the confidence intervals were
wide doesn't begin to address how silly it is to make any conclusions
about a differential effect of statins in men and women based on ASCOT.
We have evidence from other studies with more events, by the way, that
statins really do seem to have the same relative benefits in men and
women just as we would have expected had we never bothered to look.
So, when the author of the quote above writes that the FDA "looked at
the study as a whole, rather than looking at the different types of
patients in the study", the response should be that indeed that's what
the FDA did, and they did exactly the right thing.
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Lawsuit questions need for Lipitor: The ASCOT trial's 2000 women
Date: Sun, 16 Oct 2005 08:35:44 -0400
Message-ID: <dithg6$8fv$1@reader2.panix.com>
fresh~horses wrote:
> Jim Chinnis wrote:
>>You don't think there's a problem if the main study used by the TI confused
>>lots of the people treated with a statin with those treated with a placebo?
>
>
> <<lol>> When did you stop beating your wife?
Which part of what Jim Chinnis wrote do you think is incorrect?
You can see that TI relied heavily on ALLHAT For the results in women
just by looking at the table in the analysis you posted a link to.
You can read about what happened in ALLHAT in the 12/18/2002 JAMA where
the results were published (look at Table 2). It shows that about a
quarter of patients assigned to receive placebo were actually taking a
statin, and that about a quarter of patients assigned to receive a
statin were not taking it. This is presumably a much bigger problem than
even those numbers would indicate, because the people in the placebo
group who were given a statin were likely those at highest risk or with
the highest cholesterols levels.
ALLHAT (as would be expected/considered statistically correct) performed
an intention-to-treat analysis, so all the people in the placebo group
who were taking a statin were counted as if they were not taking a
statin in the analysis that found no benefit to statins.
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Lawsuit questions need for Lipitor: The ASCOT trial's 2000 women
Date: Sun, 16 Oct 2005 12:33:21 -0400
Message-ID: <ditvdh$6qr$2@reader2.panix.com>
fresh~horses wrote:
> I know what TI did because they told us; which is diametrically opposed
> to what the three study authors did. The study authors refused negative
> adverse effect information to a member of the Cochrane Collaboration.
> Indefensible. Scurillous.
You seem to be blurring two issues. The first is whether the studies
should have released their data to TI. The second (the one Jim Chinnis
and I were actually talking about) is whether the TI analysis about the
effects of statins in primary prevention in women is correct.
--
David Rind
drind@caregroup.harvard.edu
From: Chris Malcolm <cam@holyrood.ed.ac.uk>
Newsgroups: sci.med.cardiology
Subject: Re: Cholesterol Levels Are Falling, But Red Flags Are Rising
Date: 16 Oct 2005 08:14:33 GMT
Message-ID: <3regf9Fi89ucU1@individual.net>
Robert <RobertsSong@hotmail.com> wrote:
> "Chris Malcolm" <cam@holyrood.ed.ac.uk> wrote in message
> news:3r6r7lFi46urU1@individual.net...
>> Bill <xxx@yy.zz> wrote:
>>
>> > "MEM, MD" <mem2y@hotmail.com> wrote in message
>> > news:ejark192sdcmuudf0ultf9nnev8gt4uq5a@4ax.com...
>>
>> >> Something bothers me about the general theme of most of these
>> >> discussion, or maybe simply confuses me: why the focused attacks on
>> >> statins, and seemingly only statins? Yes, they make drug companies
>> >> obscene amounts of money. Yes they can lead to life-altering side
>> >> effects, and often health care providers refuse to accept these side
>> >> effects. But at the least they have shown clear cut benefits to a
>> >> wide range of patients.
>>
>> > That's correct. And more intransigent. There are people who will not
>> > concede that it is likely that statins will benefit any subgroup of
>> > people - e.g. 50+ males with diabetes and previous MIs. But believe
>> > they are all about hidden side effects and Pharma out to make big $s.
>> > In other words, you can not discuss where the balance is.
>>
>> I'm a 60+ male with diabetes who's had a heart attack. I'm convinced
>> that statins would benefit me. I'm also convinced that for me,
>> personally, they're not worth the disbenefit. When I was taking a
>> statin I lost the ability to write research papers. In other respects
>> I was still performing mentally way ahead of the average for any age,
>> and I doubt if any psychological tests could have shown a loss of that
>> kind of ability. It's an ability I've only ever had on good days. All
>> my life I've had more bad days than good days with respect to that
>> kind of mental athleticism but I've always had enough good days to do
>> the job.
>>
>> After I started taking simvastatin I had no more good days. No matter
>> how I struggled I just couldn't complete something I'd been working on
>> and half finished.
>>
>> My doc and cardiologist insisted the problem was simply age. But the
>> ability started slowly returning after I stopped the statin. It took
>> more than a year to recover to where I'd been before the statin.
>>
>> I'm sure a statin would reduce my heart attack risk. But personally
>> I'd prefer another ten years with a good brain to another twenty with
>> a once-good brain.
>>
>> I doubt if most folk would even have noticed the mental deficit I'm
>> talking about. It was roughly around the level of effect a half pint
>> of beer has on me. But for me personally it was a disbenefit that
>> wasn't worth the benefits.
>>
>> This isn't the first drug I've stopped because of what to me were
>> unacceptable side effects. A long time ago I was supposed to stay on
>> 6mg prednisolone a day for the rest of my life. At that time I
>> completely believed all the medical assurances that that dosage
>> wouldn't have the slightest cognitive effects. I sincerely believed
>> that my failing mental powers were age. I stopped the pred by tapering
>> it off very slowly for other reasons, and was amazed and delighted to
>> find my mental powers returning as the dose decreased.
>>
>> Very rare cases of extreme damage will always be controversial. I'm
>> sure that there are lots of old people taking prescription drugs who
>> quite happily accept their doctor's confident claims that the fatigue,
>> joint pains, or episodes of confusion they suffer from are just a
>> natural part of aging rather than the side effects of the drugs.
>>
>> This is *bound* to happen with drugs which are mostly prescribed to
>> old people and whose side effects mimic the common concomitants of
>> age. There's no need to do studies to find out if this *is*
>> happening. It's bound to happen unless special efforts are made to
>> stop it happening. As it happens instead of special efforts to stop it
>> happening there are extremely powerful financial incentives to deny
>> that it's happening. The aging population is a gold mine for drug
>> manufacturers.
>>
>> I'm not a statin hater. Or indeed a prednisolone hater. I just decided
>> that for me personally the disbenefits outweighed the benefits, and
>> have been rather disappointed to find how readily doctors diagnosed me
>> as suffering from age rather than their prescriptions. I don't think
>> I'm a special case with respect to that. It's a rare funeral I go to
>> where the relatives haven't stories to tell of dismissive doctoring of
>> the old fool.
>>
>> I don't think there's anything special about the statin case. It's
>> just one of at least several drugs prescribed to the elderly whose
>> side effects get swept under the carpet of age. As increasing numbers
>> of old people are put on permanent medical research is running a
>> serious risk of ending up adding to the natural symptomatology of
>> aging the natural characteristics of an over-medicated population.
>>
>> --
>> Chris Malcolm cam@infirmatics.ed.ac.uk +44 (0)131 651 3445 DoD #205
>> IPAB, Informatics, JCMB, King's Buildings, Edinburgh, EH9 3JZ, UK
>> [http://www.dai.ed.ac.uk/homes/cam/]
>>
> I understand your point and many of us actually pretty much react the same
> way. If we start a new drug and something happens then we blame it on the
> drug whether it's the drug or not.
That's not what I did. The coincidence of the cognitive problems
starting after I started taking a drug raised the possibility that the
drug might be to blame.
> The only way to find out is through studies and some science.
As it happens I am a scientist, though not a medical one. However,
you're not right that the only way to find out things like that is
through studies or science. Science is a formalisation of methods of
investigation that human beings were using successfully long before we
invented science. If science were the only way to find out things law
courts would never be able to come to a decision.
In this case, wondering if the statin might be to blame, I stopped
taking it. The cognitive problems started going away at much the same
rate as they had developed while taking the statin. I know this
doesn't *prove* that the statin caused them, but it does substantially
increase the likelihood.
> You say no
> studies have been done but they have.
You may be confusing me with someone else. I don't think I've ever
said no studies have been done. I know they have. When I first
wondered about the possibility that I was suffering from side effects
of the statin I searched Pubmed and found several relevant studies,
which I consulted. Apart from what is available on the web, as a a
university academic I have free access to medical journals. I wanted
to see whether the kind of problems I had noticed in myself had been
mentioned as possible side effects by any researchers. As I'm sure you
are aware, they have. The rate of development of the problems was also
consonant with those reported in the studies. And when I stopped
taking the statin the rate of recovery was consonant with it.
Did I have an objective way of measuring my cognitive problems? Yes,
it was very simple. My job as a university academic involves a great
deal of critical reading of difficult material, and writing some. I
found it incrasingly difficult to write research papers, and finally
doing so became impossible. Writing lecture notes, which used to be
very easy, took longer and longer, and the results were of worse
quality.
A few months after stopping the stain I found I was able to finish
some papers that I had become stuck in the middle of, unable to make
any progress. A year later I was once again writing fluently and well.
> I think you react to a new drug in a bad way no matter what that drug is.
Not at all. I'm always very pleased if my doc tells me that there's a
drug which will fix a problem he's identified. Mostly they do. And in
the case of prednisolone, I was a very enthusiastic taker of it,
because not only did it fix my problem like magic, but it actually
made me feel much better than I had done for years. I stopped it
reluctantly only because of the warnings about the risks of
osteoporosis in long term use. Discovering that minor cognitive
problems I'd been suffering from while taking it, and which both I and
my doctor had quite happily attributed to age, then ceased as soon as
I stopped it was a complete surprise.
It also didn't stop me taking it again when I had another problem for
which it was prescribed, because the problem was far more serious and
disabling than this mild cognitive impairment, and I had discovered
that that side effect completely vanished very quickly indeed as soon
as the drug was stopped.
I also get mild cognitive impairments with most pain killers, which
disappear as soon as I stop them, and which don't worry me in the
least, nor do I worry about the more serious cognitive impairments I
suffer temporarily as a result of drinking alcohol.
> I
> think if a placebo would have been given like a sugar pill then somebody
> might get the same results.
Of course they might. What makes you think I might doubt that?
> It is really a mind set that you have to keep in check.
What mind set do you think I have? I think you're confusing me with
someone who is suspicious of all drugs, and thinks they ought to be
side effect free. I expect all drugs to have side effects, and I hope
that the benefits of the drug outweigh the side effects. I know they
usually do, which is the reason why they've been licensed in the first
place.
> Medications
> obviously impact your body. When I first started taking blood pressure pills
> I felt like somebody hit me with a hammer. It takes time to adjust. There
> are always side effects to meds and it's the ration of benefit that one
> looks at.
Exactly.
> It is the quality of life issue that is important. If the quality
> of life bothers someone then that person should pursue his own happiness.
What are you trying to tell me? I started taking a statin. In the
succeeding months I started developing cognitive problems which
affected my work. I discovered that these kinds of problems had been
reported in medical journals as side effects of statins. I
experimentally stopped the statin. The problems started fading at
about the same rate at which they had developed. THe rates of
development and recovery were consonant with those reported by medical
researchers. If the problems had continued I would have had to retire
from my job. I would also have had to give up my plan of writing a
couple of books when I retired.
I consulted three doctors and a cardiologist, and Pubmed, about the
levels of risk I was personally running, and the reduction in risk I
likely to be getting from the statin. They all agreed that the
reduction of risk was about the same as I could get by taking exercise
and changing my diet. The doctors all warned me that very few people
were capable of making the requisite changes of lifestyle. I told them
to look at my medical history, in which they would find the details of
similar successful changes of diet and exercise I had made in order to
recover from injuries. They agreed that it looked as though I might be
one of the few people who coulld accomplish the necessary changes of
diet and lifestyle to realise these desired cardiovascular benefits.
I also discovered that if I took more exercise and changed my diet not
only would I reduce my risk of a heart attack by about the same as
taking a statin, I was also likely to suffer the side effect of a
healhier brain with at least a slower rate of age-related
degeneration, and possibly even a temporary cognitive improvement.
I decided it was worth making the effort. As I write this my breakfast
mackerel is baking in the oven, and after eating it I'm going to cycle
a few miles up some pretty serious hills. My searches in Pubmed, and
reading sci.med.* newsgroups, have led me to believe that doing these
kinds of things carry around the same cardiovascular benefit levels as
taking a statin.
Do you think I'm being unreasonable or unscientific about this?
--
Chris Malcolm cam@infirmatics.ed.ac.uk +44 (0)131 651 3445 DoD #205
IPAB, Informatics, JCMB, King's Buildings, Edinburgh, EH9 3JZ, UK
[http://www.dai.ed.ac.uk/homes/cam/]
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Cholesterol Levels Are Falling, But Red Flags Are Rising
Date: Sun, 16 Oct 2005 12:30:34 -0400
Message-ID: <ditv8f$6qr$1@reader2.panix.com>
Jim Chinnis wrote:
> Chris Malcolm <cam@holyrood.ed.ac.uk> wrote in part:
>
>
>>I decided it was worth making the effort. As I write this my breakfast
>>mackerel is baking in the oven, and after eating it I'm going to cycle
>>a few miles up some pretty serious hills. My searches in Pubmed, and
>>reading sci.med.* newsgroups, have led me to believe that doing these
>>kinds of things carry around the same cardiovascular benefit levels as
>>taking a statin.
>>
>>Do you think I'm being unreasonable or unscientific about this?
>
>
> I don't, FWIW.
I agree.
I think it's very hard in any individual to know whether a side effect
that comes on slowly and resolves slowly is due to a particular
medication, so I would keep an open mind about whether in this
particular case the statin was responsible for the change in mental
ability. People are wonderful at seeing cause and effect where there
isn't any, which is why blinded trials are so helpful.
But not being able to be sure that the statin was the cause doesn't make
it unreasonable for someone who seems to have had such a side effect to
decide that statins aren't worth the risk. Someone else might choose to
see whether a hydrophilic statin was better tolerated, and this would be
reasonable as well.
--
David Rind
drind@caregroup.harvard.edu
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology
Subject: Re: Cholesterol Levels Are Falling, But Red Flags Are Rising
Date: Sun, 16 Oct 2005 13:22:58 -0400
Message-ID: <diu2as$qb1$1@reader2.panix.com>
Susan wrote:
> I certainly understand that this can be true, BUT... I'm one of those
> folks who gets adverse reactions that later, upon use in the larger
> marketplace, turn out to happen to, say, .5% of all drug takers. The
> bad stuff that happens to me gets blown off by most docs (except those
> who know me for a while)as non-existent. I have to decide for myself,
> despite what studies say, what's causing what. I'm the one to live with
> the consequences.
What's hard about this is that at low levels almost all side effects get
reported with every drug and with placebo. So it doesn't necessarily
mean anything that eventually drug A turns out to have a reported rate
of conjunctivitis of say 0.5%. Even if you get conjunctivitis after
starting drug A, the association may not be causal.
On the other hand, it is certainly the case that not all side effects
are recognized in the clinical trials, or are not recognized as being as
common as they truly are. My recollection is that cough was not a known
side effect of captopril at the time it was released (despite turning
out to be very common) and sexual side effects of SSRIs were thought to
be uncommon (they probably occur in at least half of all patients).
So it's actually a tricky problem. If the side effect comes and goes
quickly with starting and stopping the drug, and it's really important
to know for sure, it's possible to do an "N of 1" trial where you get
real medicine and placebo made up for a single patient and have them
take it in a blinded fashion (typically randomly taking drug or placebo
for a week in a row). But this wouldn't work for the possible mental
side effects with statins in the OP because of the slow onset and slow
recovery he noted.
--
David Rind
drind@caregroup.harvard.edu
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Lawsuit questions need for Lipitor: The ASCOT trial's 2000 women
Date: 17 Oct 2005 18:45:01 -0700
Message-ID: <1129599901.897029.162870@z14g2000cwz.googlegroups.com>
David Rind wrote:
> fresh~horses wrote:
> > I know what TI did because they told us; which is diametrically opposed
> > to what the three study authors did. The study authors refused negative
> > adverse effect information to a member of the Cochrane Collaboration.
> > Indefensible. Scurillous.
>
> You seem to be blurring two issues. The first is whether the studies
> should have released their data to TI. The second (the one Jim Chinnis
> and I were actually talking about) is whether the TI analysis about the
> effects of statins in primary prevention in women is correct.
>
> --
> David Rind
> drind@caregroup.harvard.edu
COMMENT:
There's actually a third issue, one that is far more damning to the
question of the Therapeutics Initiative's statistical and clinical
common-sense. See http://www.ti.ubc.ca/pages/letter48.htm (table 2):
The TI *defined* a "serious adverse effect" (SAE) in such a way that
both of their groups (statin and placebo) had these SAE's at a rate of
44.2% and 43.8%, respectively. Needless to say, such an event could not
have been too serious a matter if 44% of the placebo group had it, and
total stroke, MI, and mortality in this study in both groups was under
2%. The total SAEs were not statistically different between groups (RR
1.01, CI 0.97-1.05]. However, the TI authors then decided that the two
high rates, when *subtracted* from each other, should be at least as
large as the 1.8% difference in stroke and MI between the groups (8%
vs. 9.8%), not 0.4% larger in the statin group.
They go on to compare apples and oranges by suggesting that the
"increased" statin SAEs might be making up for the decrease in stroke
and MI, despite that fact that comparing the absolute *difference*
between two large populations, with the difference between two small
populations, is a statistical no-no unless you can show they are
actually comparable things. In this case, we are being asked to
entertain the idea that if you *assume* that hospitalization for any
reason, and which was more than 4 times as common in these
participants, is *comparable* to stroke and MI, THEN the outcomes are
consistant with the idea that maybe statins do something *very bad* to
the statin group to "make up for" the stroke and MI they didn't have.
I hardly know where to begin, in discussing the unwisdom of this
argument. Except to say that no experienced physician would EVER wonder
if something that happened to 44% of the placebo group might be as bad
as stroke and MI which happens to them at a rate less than 10%, in a
study where total mortalities are even less than that. But here this
suggestion is, and this is how the TI phrases it:
"In the 2 trials where serious adverse events are reported, the 1.8%
absolute reduction in myocardial infarction and stroke should be
reflected by a similar absolute reduction in total serious adverse
events; myocardial infarction and stroke are, by definition, serious
adverse events. However, this is not the case; serious adverse events
are similar in the statin group, 44.2%, and the control group, 43.9%
(Table 2). This is consistent with the possibility that unrecognized
serious adverse events are increased by statin therapy and that the
magnitude of the increase is similar to the magnitude of the reduction
in cardiovascular serious adverse events in these populations."
COMMENT:
It's consistant with the "possibility" indeed. But so what? It's also
consistant with using a statistically insignificant flucuation in two
large groups, to paper-over a statistically significant difference in
two smaller groups. Or equally, with lumping one kind of common and
relatively benign clinical outcome, with another which is rare and
nasty and which isn't clinically equal. The first is a statistical
error, the second one a medical error. Either one is infuriating to
see, from a bunch of people who hold themselves as experts at either
statistics or medicine.
SBH
From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med.cardiology
Subject: Re: Lawsuit questions need for Lipitor: The ASCOT trial's 2000 women
Date: 18 Oct 2005 18:44:48 -0700
Message-ID: <1129686288.930511.144070@g43g2000cwa.googlegroups.com>
fresh~horses wrote:
> David Rind wrote:
> > Steve Harris wrote:
> > > COMMENT:
> > >
> > > It's consistant with the "possibility" indeed. But so what? It's also
> > > consistant with using a statistically insignificant flucuation in two
> > > large groups, to paper-over a statistically significant difference in
> > > two smaller groups. Or equally, with lumping one kind of common and
> > > relatively benign clinical outcome, with another which is rare and
> > > nasty and which isn't clinically equal. The first is a statistical
> > > error, the second one a medical error. Either one is infuriating to
> > > see, from a bunch of people who hold themselves as experts at either
> > > statistics or medicine.
> > >
> > > SBH
> >
> > Agreed. I hadn't looked at what they'd written other than the
> > meta-analysis of event rates in women, but this is a bizarre way to try
> > to compare benefits and harms. Are the authors of the letter listed
> > somewhere?
> >
> > --
> > David Rind
> > drind@caregroup.harvard.edu
>
>
>
> I think those numbers are probably a more accurate representation of
> statin side effects among those not in clincial trials.
COMMENT:
Take a look again. The "serious adverse event" rate is basically the
same for statins as placebo in these two trials. Whatever it is, it's
not a serious adverse *effect* of the DRUG, but of the disease process
itself. "Serious adverse event" if used for in a sugar pill group, is
clearly not serious adverse effect of sugar pills. Unless you believe
in really bad sugar pills.
The Therapeutics Initiative people are trying to suggest that maybe you
can subtract the SAE in one group from the other: 44.2% - 43.8% = 0.4%,
and blame the small difference in events as an EFFECT of statins (if
this was kosher, the difference would be the actual SAE DUE TO STATINS,
and is pretty low). But that's not kosher to do, because the variance
in these two large numbers is such that the difference here between
groups isn't significant. There's a very good chance that it's due to
chance. Thus, this difference can't be used for ANY purpose that lumps
it in with smaller and not equivalent clinical events. In a meta
analysis it could be used to lump in with similar endpoints to make a
stronger conclusion, but lumping hospitalization for any reason, in
with <10% MI and stroke, particularly when about 44% of everybody is
hospitalized in a study, is just not right.
SBH
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