From: sbharris@ix.netcom.com (Steve Harris  sbharris@ROMAN9.netcom.com)
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: Tricor and side effects
Date: 13 Nov 2004 18:49:35 -0800
Message-ID: <79cf0a8.0411131849.3b07bd61@posting.google.com>

COMMENT:

Here's the bad news: the fibrates are a crummy class of drugs, and
Tricor is an unusually expensive and overvalued member of the class.

The facts are that (unlike the statins) there's no data that fibrates
extend lifespan. In fact there's precious little data even that they
prevent heart attacks (I think one study with mildly positive results,
and others with none).  There's no evidence fibrates decrease cardiac
mortality. There's some epidemiologic evidence that they increase
human GI cancer risk (unlike statins).

So what do you do? Your triglycerides are quite high. But since the
drug treatment options suck, don't go there until you've failed
dietary therapy, and dietary therapy includes fish oil up to 30 grams
a day. You start with 3 capsules (grams) per meal and work your way
up. I've seen 30 g a day of fish oil bring triglyerides down to normal
from as high as 1200 mg/dL. Of course, this is no guarantee for you,
but what do you have to lose? If you use the Kirkland fishoil from
Costco, you can do 30 g a day for $21 a month. That's what, a week
worth of Tricor?

If you should fail fish oil or somehow not get max bang for the buck,
you can always try a low dose of gemfibrozil on top of it. That's the
old generic fibrate. It's a lot cheaper than Tricor and there's NO
evidence that Tricor lower triglycerides any better. So if you're
going to use a drug, at least use a cheap one. And hope the GI cancer
stuff is wrong.

Other options are to try fish oil, and top it off with a statin.
Statins don't work as well as fibrates on triglycerides by the
numbers, but they do work. And unlike fibrates, statins are actually
known to modify you risk from the disease you're treating, instead of
just fixing numbers. A statin plus niacin is also a possibility.

SBH





irfca_2000@yahoo.com (AV) wrote in message
news:<e2016115.0411120816.2118f67@posting.google.com>...

> I am 37 with a family history of CVD. My father died when he was 55
> (first attack). Brothers had heart attacks when they were 44 and 45
> but survived. I was diagnosed with Reiter's syndrome 8 years back and
> the doctor noticed elevated cholesterol and triglyceride levels. My
> triglyceride was 810.
>
> I cut down my carb intake drastically and started doing cardio
> vascular exercises. Now I am fit, jog 1 hour/day, play tennis twice a
> week, BMI of 23. While cholesterol levels are under control, this damn
> triglyceride level never goes below 600. I have been dodging taking
> pills to lower my trig. I was hoping exercise and diet will bring it
> down. But now it is inevitable.
>
> My doctor prescribed Tricor and have been taking it for the last 2
> weeks. When I did some research, I read gall bladder will be affected
> if I take Tricor. Now I am worried. In the last 6 years I have taken
> Tylenol once and Motrin twice. I am so averse to taking medications.
> Now I am forced to take Tricor for life and worried about its side
> effects.
>
> When I discussed this with my doctor, he said he doesn't even know
> whether Tricor will bring my trig level down. Only after 6 weeks he
> will know based on total lipid profile. Looks like I have to choose
> between heart disease or gall bladder problems. If you are taking
> Tricor, could you please post your views on Tricor's side effects.
>
> Thanks
> AV

From: sbharris@ix.netcom.com (Steve Harris  sbharris@ROMAN9.netcom.com)
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: Tricor and side effects
Date: 14 Nov 2004 18:20:07 -0800
Message-ID: <79cf0a8.0411141820.77845f8e@posting.google.com>

"Ed Mathes" <emathes@rochester.rr.com> wrote in message
news:<SnIld.6323$zk7.261@twister.nyroc.rr.com>...


Harris
> The facts are that (unlike the statins) there's no data that fibrates
> extend lifespan. In fact there's precious little data even that they
> prevent heart attacks (I think one study with mildly positive results,
> and others with none).  There's no evidence fibrates decrease cardiac
> mortality. There's some epidemiologic evidence that they increase
> human GI cancer risk (unlike statins).

EM
>>The Helsinki Heart study (4081 patients) and VA-HIT trial (2531 men)
were placebo controlled trials using gemfibrozil. In HHS, there was a 34%
reduction in "cardiac events", in VA-HIT there was a 24% reduction in the
combined outcome of death from coronary heart disease, nonfatal
myocardial infarction, and stroke (P<0.001).<<


COMMENT:

Ed, I said there's no evidence for reduction in cardiac mortality with
fibrates, and there isn't. Period.

The VA-HIT did NOT show reduction in cardiac deaths. You have to fold
in the non-fatal MIs with the deaths to get a significant number
there, and that's what they did. But that's cheating, because it's
stone soup, and most of your significance is coming from non-fatal
events. Big deal. And that's the best result out there for any large
fibrate study. Moreover, not only was there no reduction of cardiac
mortality in VA-HIT or HHS, but none also for all-cause mortality.
Also, if you do meta-analysis of all controlled fibrate studies
(>20,000 patients), you get the same results as regards all-cause
mortality and even cardiac-mortality, so this is not a study power
problem.

It's also hardly fair to cherry-pick your fibrate sub-results like
that. You want to cherry pick your small studies with non-significant
results for the significant clinical events, and significant results
for the less significant clinical events. Okay, but I can do better at
that game. In the biggest and longest randomized fibrate trial that
exists, the WHO cooperative trial (10,000 patients for more than 5
years) using clofibrate, there was a statistically significant (P <
0.01) 25% *excess* total mortality in the fibrate group vs. placebo.
Nearly all causes but violent and accidental deaths went up, in the
fibrate treatment group. That study is 150,000 patient-years, 100
times the size of your diabetes study in patient-years. Sure, it's
possible some fibrates are better or worse than others, and it's
possible they work better in some patients (diabetics) than others,
but remember that doesn't help you if so. We're talking to a guy who
has no particular health problems, being put on Tricor, for which
there are no data worth mentioning, for primary prevention, which is
an unproven use to say the least. The FDA approves these rotten drugs
based on a proxy variable (triglyceride reduction) and we know what
disasters that can lead to (remember the antiarrhythmic drug fiasco?).

So we're left with our original problem. Here's the dialog between
doctor and intelligent layman:

Patient: Doc, should I take this "Tricor"? It's expensive, but will it
save my life?

Doc. It might prevent you from having heart attack. A related fibrate
drug did, in 2 big studies.

Patient: Related fibrate, you say? So I presume that all these
"fibrate" drugs are the same, or else you wouldn't be giving me data
on one, to support use of another?

Doc. Good question. Well, I have to admit that another related fibrate
called clofibrate actually killed some patients in the biggest trial
with these fibrate drugs that exists, so the answer is "no." They
aren't the same. I sure hope they're not, anyway!

Patient: Hmmm. Well, doc, then I want the specific one that prevented
the heart attacks!  Is that this "Tricor"?

Doc: No. It was another one called Lopid or gemfibrozole.

Patient. Well, does Tricor prevent heart attacks like gembribrozil, or
does it kill people, like clofibrate?

Doc. We don't know. There are no large and long studies of Tricor
looking at that.

Patient: Well, why are you giving me Tricor then??

Doc. The drug rep left some free samples.

Patient: No thanks!!  I want that other stuff, the gemfibrozil. It's
more expensive, I bet.

Doc. No, gemfibrozole is generic and quite a lot cheaper.

Patient. Great!  I can save money and my life at the same time!

Doc. I didn't say it would save your life.

Patient: What? Gemfibrozil prevented heart attacks but didn't save any
lives? Isn't that mighty peculiar?

Doc. I guess so. Maybe the studies weren't big enough or lasted long
enough

Patient: Well, you said they were big!  How many people were in them
and how long did they last?

Doc.  Oh, around six thousand people, and five years.

Patient. That's 30,000 patient-years! If they didn't save any lives in
that time, I'll bet it's because they were doing something else nasty
to make up for the heart attacks. How big was that clofibrate study
where the nasty things happened and the patients died?

Doc. [looking furiously at medline and cursing these patients who take
up half an hour for a 10 min office visit]: Okay, it was 150,000
patient-years.

Patient. 150,000! Golly. How about I just forget it, and live with the
high triglycerides? Isn't there any other way to get them down?

Doc. Well, you could eat a lot of salmon or salmon oil.

Patient: You're kidding. Will that do it?

Doc. Yes. There are other studies to indicate that.

Patient: Will that save my life?

Doc: Nobody knows. There exist no big studies to say, either way.

Patient: Why not? It sounds like a great thing to study.

Doc: Drug companies fund the studies, and they don't make fish at
Pfizer.

Patient: Hah, hah, fish at Pfizer. Look, doc, I think I'd rather take
my chances with the fish, so long as it gets the triglycerides down. I
mean, I'm not sick, so we're treating a number anyway, right? Why not
treat it with a food rather than a drug from a class of drugs, one of
which already been demonstrated to kill patients, and the one you want
to treat me with hasn't been tested any better than the fish? And is a
lot more expensive than fish. Say, why didn't you tell me about that
up front?

Doc. Look, Mr. Smith, I'm a physician. I write prescriptions. If you
want a change in diet, you have to see the Naturopath down the street.
Those guys are quacks, though.

Patient: [under his breath, as he's leaving] I'll be the judge of
who's the quack.

================================================
Ed:

>Finally, UK-HDL-C Consensus Group issues a statement on fibrate use in
>3/2004:
>
>        Fibrates should be used in patients with certain lipid
>abnormalities, where lifestyle changes have failed to correct these
>abnormalities. In particular, they should be prescribed for:

<Snip English blather>

COMMENT:

One man's "lifestyle change" is another man's "impossible diet."  Try
the salmon oil caps if it's the numbers you're fixing.  But there's
still no reason to think these drugs save lives. If they couldn't
prove it with a total of 200,000 patient-years of studies, I think
they're up a creek.

And finally, along that line, let me give you a heads-up about
"Consensus Groups".  The reason they exist in the first place is that
there isn't any consensus. <g>. If there was, there wouldn't be a need
for a consensus group.  Nor does the consensus group help much to
*create* consensus if the science isn't there. Which is the case with
fibrates.  Unless you are creating a consensus only among people who
just want to look to people in authority, and never bother to look at
the primary studies themselves. Which isn't you or me, is it? See the
three abstracts appended for more.

SBH


1. Curr Opin Lipidol 2000 Dec;11(6):609-14

Hypertriglyceridemia and the fibrate trials.

Faergeman O.

Department of Medicine & Cardiology, Aarhus Amtssygehus
University Hospital, Aarhus, Denmark.

Epidemiological studies published since 1996 have established that
hypertriglyceridemia can predict risk of cardiovascular disease in a
manner statistically independent of HDL cholesterol. Nevertheless,
the relationship of concentrations of plasma triglycerides to risk of
cardiovascular disease remains less than straightforward, partly
because triglycerides are carried in lipoproteins of different
atherogenicity, partly because hypertriglyceridemia is
associated with non-lipid atherogenic and thrombogenic processes.
For example, the association of highest risk of cardiovascular
disease to moderate rather than to severe hypertriglyceridemia
can be understood in terms of the distribution of triglycerides
between different classes of plasma lipoproteins. It is
counter-intuitive
to most clinicians, however, and hence it can result in the
misdirection
of clinical efforts including drug therapy. Fibrates lower plasma
triglycerides, and raise HDL, efficiently and with few immediate
side-effects. Central to their mode of action is activation of certain
nuclear receptors in cells. There is no necessary connection,
however, between that fascinating biochemistry and clinical
benefit as defined by reductions in rates of death by coronary
artery disease. A review of trials of cholesterol-lowering by
diet and drugs, published between 1966 and 1996, included
12 trials of therapy with fibrates or placebo in more than 21000
patients. Overall, these trials indicated no benefit in terms of
reduction in risk of coronary deaths. The period since 1996
has seen the publication of four additional trials of
treatment of 6144 patients with fibrates or placebo. Two of
them were major trials. The VA-HIT was very encouraging,
because treatment with gemfibrozil produced a significant
reduction in the combined incidence of fatal and non-fatal
coronary events.  There was no significant reduction in coronary
deaths, however. The results of BIP were frankly disappointing,
because they
demonstrated no significant effect of treatment with bezafibrate
on either the primary end-point of the trial or on rates of coronary
death. Clinical indications for the use of fibrates can obviously
not be based on biochemical insights, however intriguing in
their own right, but they have also not been satisfactorily defined
by the randomized clinical trials published to date. Hope
remains, however, that some clarification will result from
ongoing trials of fibrate treatment of patients with type II
diabetes.

Publication Types:
Review
Review, tutorial

PMID: 11086334 [PubMed - indexed for MEDLINE]




2: J Intern Med. 1994 Jan;235(1):31-9.

Comment in:
    J Intern Med. 1994 Jan;235(1):1-4.

The Helsinki Heart Study: an 8.5-year safety and mortality follow-up.

Huttunen JK, Heinonen OP, Manninen V, Koskinen P, Hakulinen T, Teppo
L, Manttari M, Frick MH.

National Public Health Institute, University of Helsinki, Finland.

OBJECTIVES. Earlier monitoring of all symptoms, hospital admissions,
cancer diagnoses and causes of death during gemfibrozil treatment had
raised some suspicions which called for further follow-up. DESIGN. Close
monitoring of selected, potentially adverse events amongst treated
subjects after a placebo-controlled trial and comparing occurrences to
those in various untreated groups. SETTING. All participants of the
Helsinki Heart Study (a controlled, 5-year, multi-clinic coronary heart
disease (CHD) primary prevention trial with gemfibrozil and placebo) were
offered gemfibrozil treatment and twice yearly follow-up for 3.5 years.
Untreated groups in the source population and national cancer statistics
were utilized in comparisons. SUBJECTS. Of the 2046 dyslipidaemic men
initially randomized to gemfibrozil, 2002 survivors entered the 3.5-year
follow-up; of the 2035 initial placebo men, 1992 continued to be
monitored. INTERVENTIONS. Gemfibrozil was chosen for the follow-up by
66.3% of the gemfibrozil-treated and 68.5% of the placebo-treated men.
MAIN OUTCOME MEASURES. Gastrointestinal symptoms, surgery, strokes,
cancer incidence, mortality by cause. RESULTS. Gastrointestinal symptoms
remained more common in the original gemfibrozil group. After 8.5 years
strokes numbered 32 (gemfibrozil) vs. 37 (placebo), violent deaths 16 vs.
14, and cancers 51 in both groups. Total mortality was equal during the
original 5 years, but higher in the gemfibrozil group post-trial, leading
to an 8.5 year mortality of 101 vs. placebo 83 (P = 0.19). This was
mainly a result of higher cancer mortality in the gemfibrozil (30) than
the placebo group (18, P = 0.08). An additional 18-month post-study
registry follow-up disclosed 13 placebo and five gemfibrozil cancer
deaths, altering the cancer mortality to gemfibrozil 35 vs. placebo 31 at
10 years. CONCLUSIONS. The most plausible explanation for the discrepancy
between cancer incidence and cancer-specific mortality, based mainly on
comparison with untreated groups, is delayed diagnosis. The increased
cancer and total mortality is most probably due to chance, based on the
later reversal of trends.

Publication Types:
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 8283157 [PubMed - indexed for MEDLINE]


3 : Lancet. 1980 Aug 23;2(8191):379-85.

W.H.O. cooperative trial on primary prevention of ischaemic heart disease
using clofibrate to lower serum cholesterol: mortality follow-up. Report
of the Committee of Principal Investigators.

[No authors listed]

This is a further report on the mortality amongst men in the W.H.O.
cooperative trial of the primary prevention of ischaemic heart disease
(IHD) by clofibrate.  Mean observation was 9.6 years, 5.3 in the trial
and 4.3 afterwards; 911 deaths are recorded in 150 000 man-years. There
were 25% more deaths in the clofibrate-treated group than in the
comparable, high serum cholesterol, control group (p < 0.01), and there
was an excess in the treated group in all the three participating
centres. Mortality from all causes was higher in the treated group than
in the high cholesterol controls during the trial, equal in the first two
years after leaving the trial, but higher again after that. No particular
disease accounted for the overall excess: the treated group had more
deaths from IHD, stroke, cancer, and other major diseases though most of
these differences were not individually significant. There was no excess
in deaths due to accidents and violence. There was also a significant
excess in the death rate from all causes, and from causes other than IHD,
in the treated group compared with the second, low cholesterol, control
group. No relationship could be shown between the excess mortality and
cholesterol reduction, or the length of time on clofibrate. Explanation
of the excess mortality is not apparent: a long term toxic effect of
clofibrate, the possible consequences of reducing body cholesterol pools
and, remotely, chance have all to be considered.

Publication Types:
    Clinical Trial
    Randomized Controlled Trial

PMID: 6105515 [PubMed - indexed for MEDLINE]

From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: Tricor and side effects
Date: Sun, 14 Nov 2004 23:23:44 -0500
Message-ID: <cn9b44$g21$1@reader1.panix.com>

Ed Mathes wrote:
> So, Dr. Harris, what do you propose then for patients who don't tolerate
> statins?  Remember, although primarily triglyceride drugs, fibrates also
> have effects on other cholesterol parameters.
>
> Ed

Dr. Harris can give his own answer, but my take on this is that in
patients who don't tolerate statins we're in the same situation we were
before the statins were available: there is no evidence that any of the
other cholesterol-lowering medications are of benefit in primary
prevention, and several studies suggest these drugs cause harm.

In secondary prevention, using a fibrate or niacin is a reasonable
option (though one that doesn't get you enormous benefits). In primary
prevention, you mostly need to accept that we don't have any medications
other than statins that have been show to work.

--
David Rind
drind@caregroup.harvard.edu

From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: Tricor and side effects
Date: Sun, 14 Nov 2004 23:20:01 -0500
Message-ID: <cn9at9$fv4$1@reader1.panix.com>

Ed Mathes wrote:
> Thanks David...the first paragraph quoted below is from Steve Harris.
>
> I was just posting the (few) fibrate studies..
>
> DAIS was an interesting study using fenofibrate vs. placebo.
> Small study, but there was a "trend" toward benefit in the fenofibrate
> group.
> I think this is important if you have a patient that can't tolerate a
> statin.
>
> As a branch off this.....a fair number of patients aren't on "just a
> statin"...
> many are on an ACE or ARB, a beta-blocker, diuretic, in combination
> with fenofibrate or tricor, lots more on Zetia, and many many on diabetes
> meds.
>
> What is the overall contribution of these meds together?
> Is the "risk reduction" additive or do you reference the med with the
> "greatest effect"?
> Is there a ceiling or cap on risk reduction?
> Is it lower than 100% risk reduction (I am speaking theoretically for the
> concrete thinkers out there...nothing is 100% except death and taxes).
>
> Ed

If we're talking about cholesterol lowering meds, we don't know the
effect on mortality or cardiovascular events of the drugs in
combination. So even though the Zetia reps may be telling you how
wonderful it is in combination with a statin, there are no published
studies with clinical endpoints showing the combination to be beneficial
compared with a statin alone. (I believe there are trials underway
looking at this issue, so we may have an answer soon.)

--
David Rind
drind@caregroup.harvard.edu

From: sbharris@ix.netcom.com (Steve Harris  sbharris@ROMAN9.netcom.com)
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: Tricor and side effects
Date: 16 Nov 2004 18:17:02 -0800
Message-ID: <79cf0a8.0411161817.1bcb2239@posting.google.com>

"Ed Mathes" <emathes@rochester.rr.com> wrote in message
news:<ukVld.6059$Mg.2023@twister.nyroc.rr.com>...

> Admonished.......
>
> I don't believe I expressed an opinion on fibrates.
>
> If I use a fibrate, I use Tricor (FENOFIBRATE), believing it is safer than
> gemfibrozil  (Kevlar Body Armor on), and then only rarely.


COMMENT:

There's some epidemiological evidence suggesting that fenofibrate may
cause less rhabdomyolysis than gemfibrozil, but it's heavily
contaminated by the number of cases of statin+fibrate rhabdo, and in
particular those from the statin Baycol, which has since been recalled
for this reason. Epidemiological evidence (as opposed to controlled
prospective trials) is of secondary value, and here it's badly
contaminated evidence. There's no more Baycol, and it's epidemiology.
Would even the epidemiology hold up for the other statins?  How about
for no statin?  And remember, it requires you to use fenofibrate,
which we have a lot less study safety data for, so for all we know,
Tricor is the Baycol of tomorrow. None of this makes me happy. To each
his own, but I vote for the less expensive and best studied fibrate
(gemfibrozil) if you feel you're stuck using one. Which would be only
where fish and statins fail.



>
> You didn't comment on The Diabetes Atherosclerosis Intervention Study
> (DAIS).
>     Endpoints reported:
>       a.. Death: Fenofibrate, 6; placebo, 9
>       b.. MI: Fenofibrate, 9; placebo, 12
>      c.  Coronary angioplasties: Fenofibrate, 5; placebo 12
>      d.. Coronary bypass operations: Fenofibrate, 14; placebo, 18
>
> Also, the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD)
> trial is due to complete this year.
>
> So, Dr. Harris, what do you propose then for patients who don't tolerate
> statins?  Remember, although primarily triglyceride drugs, fibrates also
> have effects on other cholesterol parameters.
>
> Ed


Comment;

The problem with the study above is the results aren't significant,
and could be due to chance. So what do we do with them?

The fact that this is diabetics makes me want to believe them. If
there's any group in "primary prevention" that acts like it's a
secondary prevention group, it's diabetics. The statin trials
certainly show this clearly and statistically significantly. So it may
be true. But we don't yet know. Whatever the results are, they apply
only to diabetics, which are probably a special primary prevention
group.

There are patients who don't tolerate statins. But it's rare that they
don't tolerate any of the major statins at any dose that does any
good. And you still have to try fish oil.

Why fish oil?  Well, because fish oil really has been found to prevent
death in a prospective study in a secondary prevention trial, unlike
any fibrate. And it lowers triglycerides by 40% typically, which is
pretty good. And it's cheap. So I wouldn't even think of a fibrate
unless the patient had failed statins AND fishoil (maybe they're a
"rather die than not be vegan" sort).


QJM. 2003 Jul;96(7):465-80.

The role of omega-3 fatty acids in the secondary prevention of
cardiovascular disease.

Lee KW, Lip GY.

Haemostasis, Thrombosis and Vascular Biology Unit, University Department
of Medicine, City Hospital, Birmingham, UK.

It has long been recognized from epidemiological studies that Greenland
Eskimos have substantially reduced rates of acute myocardial infarction
(MI) compared with Western controls. From these epidemiological
observations, the benefits of fatty fish consumption have been explored
in cell culture and animal studies, as well as randomized controlled
trials investigating the cardioprotective effects of omega-3 fatty acids.
Dietary omega-3 fatty acids seem to stabilize the myocardium
electrically, resulting in reduced susceptibility to ventricular
arrhythmias, thereby reducing the risk of sudden death. These fatty acids
also have potent anti-inflammatory effects, and may also be
antithrombotic and anti-atherogenic. Furthermore, the recent
GISSI-Prevention study of 11 324 patients showed a marked decrease in
risk of sudden cardiac death as well as a reduction in all-cause
mortality in the group taking a highly purified form of omega-3 fatty
acids, despite the use of other secondary prevention drugs, including
beta-blockers and lipid-lowering therapy. The use of omega-3 fatty acids
should be considered as part of a comprehensive secondary prevention
strategy post-myocardial infarction.

Publication Types:
    Review
    Review Literature

From: sbharris@ix.netcom.com (Steve Harris  sbharris@ROMAN9.netcom.com)
Newsgroups: sci.med.cardiology,sci.med
Subject: Re: Tricor and side effects
Date: 18 Nov 2004 13:36:24 -0800
Message-ID: <79cf0a8.0411181336.6e47fbf@posting.google.com>

"Ed Mathes" <emathes@rochester.rr.com> wrote in message
news:<MPymd.378$Uf.255@twister.nyroc.rr.com>...

> Thank you...but of note, gemfibrozil is associated with a higher rate of
> rhabdo than Tricor when used in conjunction with statins.

COMMENT:

Yes, but again I'd like to know of evidence that that's still true
when the Baycol data is removed.


> We already recommend fish oil in our practice.


Good for you. Do you recommend enough of it? It's about 30% EPA+DHA
and it takes around 3 grams of EPA+DHA to get a good effect. That's 7
oz of salmon or about 9 capsules.



> And was it not the inappropriate use of Baycol and gemfibrozil in
> combination that caused all the uproar, not Baycol alone?


In a third of the cases it was Baycol+gemfibrozil, and 2/3rds of them,
Baycol alone.


SBH

From: sbharris@ix.netcom.com (Steve Harris  sbharris@ROMAN9.netcom.com)
Newsgroups: sci.med.cardiology,sci.med,alt.support.diabetes,rec.food.cooking
Subject: Re: Tricor and side effects
Date: 18 Nov 2004 13:51:34 -0800
Message-ID: <79cf0a8.0411181351.164d4dfb@posting.google.com>

"Dr. Andrew B. Chung, MD/PhD" <andrew@heartmdphd.com> wrote in message
news:<1100529306.ghI4DRtNXozHfRGslYVoIA@teranews>...
> David Rind wrote:
>
> > Ed Mathes wrote:
> > > So, Dr. Harris, what do you propose then for patients who don't tolerate
> > > statins?  Remember, although primarily triglyceride drugs, fibrates also
> > > have effects on other cholesterol parameters.
> > >
> > > Ed
> >
> > Dr. Harris can give his own answer, but my take on this is that in
> > patients who don't tolerate statins we're in the same situation we were
> > before the statins were available: there is no evidence that any of the
> > other cholesterol-lowering medications are of benefit in primary
> > prevention, and several studies suggest these drugs cause harm.
> >
> > In secondary prevention, using a fibrate or niacin is a reasonable
> > option (though one that doesn't get you enormous benefits). In primary
> > prevention, you mostly need to accept that we don't have any medications
> > other than statins that have been show to work.
> >
> > --
> > David Rind
> > drind@caregroup.harvard.edu
>
> Yes, David, you are correct that the story concerning the benefit of using
> non-statin lipid lowering medications for primary prevention is not complete.
>
> However, fenofibrate either singly or in combination with statins will
> likely to have a role in primary prevention of atherosclerosis in folks
> with Metabolic Syndrome (MetS) who have insulin resistance and secondary
> prevention of atherosclerosis in folks with Type 2 Diabetes.
>
> This is suggested by DAIS as cited by Ed Mathes.


COMMENT:

It is not. At best the DAIS findings "suggest" a role for fibrates in
diabetics, but even that's not proven. By the time you get to people
with metabolic syndrome, you're way down on the evidence curve. It's
hard enough even to show that statins save lives when you're doing
primary prevention in people who merely have metabolic syndrome, but
not yet frank diabetes. For fibrates, you're in even worse trouble.




 There is a case to be made
> for being proactive here and not wait for "definitive" trials because these
> folks are at high risk for cardiovascular events.  I would commend Ed for his
> position which is one of concern for his patients.


COMMENT:

His concern for his patients has nothing to do with it. Part of
concern in medicine is "first, do no harm." Gemfibrozil has had at
least 20,000 patient-years of placebo controlled trial to show that it
prevents heart attack death or death in people with "metabolic
syndrome." It has failed. Do you know how much 20,000 patient years of
gembribrozil costs, Andrew?  Something on the high side of $10
million.  Any "definitive trials" showing it saves lives will
certainly show it costs more than $10 million per life to do it, if at
all. And will be lucky if they don't show it (on net) kills people,
like clofibrate.

There are opportunity costs in medical care. $10 million you spend
here is $10 million you don't get to spend there. Even if Ed is very
lucky and gemfibrozile does save lives and it's only $10 million per
life, there are better ways to spend the money in medicine. I can
think of many, many areas of preventive medicine in which you can save
certainly more than one life for $10 million.


SBH

From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med.cardiology,talk.politics.medicine,sci.med
Subject: Re: JAMA on FDA & PHARMA: Lack of vigilance, lack of trust
Date: Wed, 24 Nov 2004 21:47:55 -0500
Message-ID: <co3h51$4uf$1@reader1.panix.com>

Ed Mathes wrote:
> David:  Regarding Zetia.  EASE demonstrated an additional 23% reduction
> in LDL when ezitimibe is added to a statin.
> True, there is no hard endpoint data yet available.

There are several trials showing additional LDL lowering when ezitimibe
is added to a statin. The problem is that we don't know that that means
that ezitimibe does anything useful or is even safe. No one feels better
just because their LDL is lower. Remember that niacin and the fibrates
appeared to increase total mortality when given for primary prevention,
despite favorable effects on lipids.

I'm not raising this just to make debating points. I think people should
be very hesitant to prescribe anything other than a statin for primary
prevention until we have some studies showing clinical benefits. If you
tell me you're caring for a 45 yo male smoker with hypertension who had
three brothers die of MIs at age 47, and you can't get his LDL below 170
with 80 mg of atorvastatin, I'd probably say roll the dice and add
ezitimibe. But that's the sort of clinical scenario it would take to get
me to prescribe a non-statin for primary prevention in the absence of
clinical endpoint studies. And I'd do it knowing that I had essentially
no evidence to support my decision -- that I was just making a guess
that it might be helpful in a person at sky high risk for having a bad
cardiovascular event.

--
David Rind
drind@caregroup.harvard.edu