The role of fibrates in the prevention of cardiovascular disease—a pooled meta-analysis of long-term randomized placebo-controlled clinical trials

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MarilynMann - 30 Oct 2007 14:32 GMT

American Heart Journal, Volume 154, Issue 5, Pages 943-953 (November
2007)

The role of fibrates in the prevention of cardiovascular disease—a
pooled meta-analysis of long-term randomized placebo-controlled
clinical trials

Sandeep Ajoy Saha, MD, Lenney G. Kizhakepunnur, BS, Amol Bahekar, MD,
Rohit R. Arora, MD, FACC, FAHA

Background
Fibrates are effective antilipidemic agents with peroxisome
proliferator–activated receptor agonist activity, but clinical trial
data on their role in cardiovascular prevention are conflicting. We
conducted a systematic review and meta-analysis of randomized clinical
trials to evaluate their role in prevention of cardiovascular events.

Methods
A total of 36489 patients from 10 published randomized placebo-
controlled trials were analyzed using the Mantel-Haenszel fixed-
effects model. Odds ratios were computed for cardiovascular outcomes
from data pooled from the selected trials, and statistical
significance was tested using the z-test statistic (2-sided α error <.
05).

Results
Fibrates significantly reduced plasma total cholesterol and
triglyceride levels by about 8% and 30%, respectively, and raised high-
density lipoprotein cholesterol levels by about 9% compared with
placebo. The odds of all-cause mortality tended to be higher (P = .
08), and the odds of noncardiovascular mortality were significantly
higher (P = .004) with the use of fibrates. However, these significant
differences did not persist after exclusion of trials using clofibrate
as the study drug. Fibrates did not significantly reduce the odds of
cardiovascular mortality (P = .68), fatal myocardial infarction (MI)
(P = .76), or stroke (P = .56). On the other hand, fibrates
significantly reduced the odds of nonfatal MI by about 22% (P < .
00001). The odds of developing cancer were not significantly higher
with the use of fibrates (P = .98), nor were the odds of cancer-
related death (P = .17).

Conclusions
In conclusion, our meta-analysis revealed that the long-term use of
fibrates significantly reduces the occurrence of nonfatal MI but has
no significant effect on other adverse cardiovascular outcomes.

Department of Medicine, Chicago Medical School, Chicago, IL

Reprint requests: Sandeep Ajoy Saha, MD, Division of Cardiology,
Chicago Medical School and North Chicago VA Medical Center, 3001 Green
Bay Road, North Chicago, IL 60064.

* * *
This is an example of why I don't think the FDA should approve drugs
solely based on their effect on lipids.

Marilyn

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bigvince - 30 Oct 2007 14:54 GMT

> * * *
> This is an example of why I don't think the FDA should approve drugs
> solely based on their effect on lipids.
>
> Marilyn

CLINICIAN'S CORNER
Drug Treatment of Hyperlipidemia in Women
Judith M. E. Walsh, MD, MPH; Michael Pignone, MD, MPH

JAMA. 2004;291:2243-2252.

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. "

Do you feel the evidence of benefit is adequate to treat women with
statins

Thanks Vince

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MarilynMann - 30 Oct 2007 15:16 GMT

> > * * *
> > This is an example of why I don't think the FDA should approve drugs
[quoted text clipped - 60 lines]
>
> Thanks Vince

I assume you mean for primary prevention? If their risk level is high
enough, yes.

Marilyn

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Jim Chinnis - 30 Oct 2007 16:37 GMT

MarilynMann <mannm@comcast.net> wrote in part:

>> > * * *
>> > This is an example of why I don't think the FDA should approve drugs
[quoted text clipped - 63 lines]
>I assume you mean for primary prevention? If their risk level is high
>enough, yes.

That's exactly right. All the data on statins show a remarkably constant
relative reduction in heart disease outcomes across levels of absolute risk.
At some point, absolute risk becomes high enough that the benefits of
statins exceed their risks. In large studies, we talk about primary and
secondary prevention. But in real life, everyone is an individual. Some
people who'd be classified as "primary prevention" in a study actually have
very high absolute risk, while some classified as "secondary" have low
absolute risk.
--
Jim Chinnis Warrenton, Virginia, USA

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Jim Chinnis - 30 Oct 2007 16:32 GMT

MarilynMann <mannm@comcast.net> wrote in part:

>In conclusion, our meta-analysis revealed that the long-term use of
>fibrates significantly reduces the occurrence of nonfatal MI but has
[quoted text clipped - 9 lines]
>This is an example of why I don't think the FDA should approve drugs
>solely based on their effect on lipids.

Yes.
--
Jim Chinnis Warrenton, Virginia, USA

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