Bezafibrate Infarction Prevention Study - BIP
The goal of the trial was to evaluate treatment with the fibric acid derivative bezafibrate compared with placebo in patients with coronary artery disease.
Bezafibrate would be more effective in preventing death or myocardial infarction (MI).
- Placebo Controlled
Patients Screened: 15,524
Patients Enrolled: 3,090
Mean Follow Up: 16 years
Mean Patient Age: 60 years
- Patients 45-74 years of age with a history of MI and/or angina
- Total cholesterol 180-250 mg/dl, triglyceride <300 mg/dl, LDL-C <180 mg/dl, and HDL-cholesterol <45 mg/dl
- Congestive heart failure (New York Heart Association class III-IV)
- Unstable angina within the last 3 months
- Coronary artery bypass grafting or percutaneous transluminal coronary angioplasty within the last 6 months
- Cerebrovascular disease
- Insulin-dependent diabetes
- Contraindications to use of bezafibrate
- Nonfatal MI, fatal MI, or sudden death
- Unstable angina
- All-cause mortality
- Cardiovascular mortality
Patients with coronary artery disease were randomized to bezafibrate (n = 1,548) versus placebo (n = 1,542).
At baseline, the use of aspirin was 71%, angiotensin-converting enzyme inhibitor was 12%, beta-blocker was 38%, calcium antagonist was 50%, and nitrate was 51%.
Overall, 3,090 patients were randomized. The mean age was 60 years, 9% were women, body mass index was 27 mg/m2, prior MI was present in 79%, mean total cholesterol was 212 mg/dl, triglyceride was 145 mg/dl, high-density lipoprotein cholesterol (HDL-C) was 35 mg/dl, and low-density lipoprotein cholesterol (LDL-C) was 148 mg/dl.
At a mean follow-up of 6.2 years, the primary endpoint, fatal or nonfatal MI or sudden death, was 13.6% in the bezafibrate group versus 15.0% in the placebo group (p = 0.26). For individual outcomes, all-cause mortality was 10.4% versus 9.9% (p = 0.62), MI was 9.7% versus 11.2%, and stroke was 4.6% versus 5.0% (p = 0.66), respectively for bezafibrate versus placebo. There was no difference in adverse events, including cancer, between the treatment arms.
At 16 years, the cumulative incidence of death was 35.3% in the bezafibrate group versus 37.9% in the placebo group (p = 0.12). With multivariate analysis, there was a marginally significant 11% reduction in mortality with the use of bezafibrate (p = 0.06). This benefit was most pronounced among those with >8 mg/dl increase in HDL-C (hazard ratio [HR] 0.78, p = 0.008) versus those with <8 mg/dl increase (HR 0.95, p = 0.43).
Among coronary artery disease patients with a mean HDL-C of 35 mg/dl and a mean LDL-C of 148 mg/dl, the use of bezafibrate for approximately 6 years was not associated with a reduction in adverse events during this initial follow-up period. When follow-up was extended to 16 years, there was a marginally significant reduction in mortality with the use of bezafibrate. This benefit was most pronounced among those with greater than 8 mg/dl increase in HDL-C. Unfortunately, very few women were studied in this trial.
In current practice, the patients represented in this trial (prior MI and LDL-C >100 mg/dl) would have been primarily treated with a statin medication. It is unknown what the comparative effects of a fibrate medication versus a statin medication versus the combination of these two medications would be in these patients.
The VA-HIT trial studied patients with coronary artery disease, who had low HDL-C (≤40 mg/dl), and LDL-C (≤140 mg/dl). That trial documented a 22% reduction in death or MI with the use of gemfibrozil. Further studies examining HDL rising with fibrate medications are necessary.
Goldenberg I, Boyko V, Tennenbaum A, Tanne D, Behar S, Guetta V. Long-term benefit of high-density lipoprotein cholesterol-raising therapy with bezafibrate: 16-year mortality follow-up of the bezafibrate infarction prevention trial. Arch Intern Med 2009;169:508-14.
The BIP study group. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease. Circulation 2000;102:21-7.
Presented at the European Society of Cardiology, Vienna, 1998
Keywords: Cholesterol, Myocardial Infarction, Stroke, Multivariate Analysis, Follow-Up Studies, Body Mass Index, Gemfibrozil, Death, Sudden, Lipoproteins, Bezafibrate, Triglycerides
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