Bezafibrate therapy was associated with significant long-term cardiovascular protection after extending follow-up on a previous study, according to a study published on the Jan. 29 issue of the Journal of the American College of Cardiology.
The researchers said that the exclusion of high-risk patients, such as those with diabetes and high levels of blood glucose, might have skewed the results because fibrate therapy has been shown to be more effective. The results of that earlier study were published in the July 4, 2000 issue of Circulation: Journal of the American Heart Association.
In this trial, Ilan Goldenberg, MD, of the Heart Institute at Sheba Medical Center in Tel Hashomer, Israel, and colleagues, adjusted risk for the combined end point of cardiac death or nonfatal MI during an extended mean 8.2-year follow-up period of the BIP trial was assessed in 3,090 patients allocated to the original bezafibrate (1,548 participants) and placebo (1,542 participants) groups of the trial.
The combined primary endpoint of cardiac death or nonfatal MI occurred in 276 (17.8%) of the bezafibrate patients and 313 (20.3%) of those taking placebo, according to authors.
The initial Bezafibrate Infarction Prevention (BIP) trial randomized 3,090 participants to bezafibrate 400 mg a day or placebo from May 1990 through January 1993. The results yielded a nonsignificant 7.3% reduction in the rate of major cardiac events after a mean follow-up period of 6.2 years, despite increases in HDL cholesterol and decreases in triglycerides.
During the extended follow-up period, the researchers reported that non-study LLDs were administered to a significantly greater proportion of placebo-allocated patients (57%) than bezafibrate-allocated patients (53%).
The authors wrote that their analysis demonstrated that the benefit of bezafibrate therapy was pronounced (18% risk reduction) without or before treatment with non-study LLDs initiated during follow-up and attenuated after therapy with non-study LLDs initiated during the observation period. Treatment with bezafibrate was shown to be associated with a significant 17% risk reduction when study patients were censored from the analysis upon initiation of therapy with non-study LLDs, the researchers said.
Though the reductions were significant, beneficial effects of the drug were significantly lessened in patients with advanced heart failure or ischemic symptoms, but the reason for this effect remains unclear, Goldberg and colleagues said.
They noted that the beneficial effects of bezafibrate were found only after adjusting for the use of nonstudy lipid-lowering medications. "Therefore, further studies are needed to determine the incremental benefit of fibrates in the current era of widespread statin use for secondary prevention in [coronary heart disease] patients," the authors concluded.