Secondary prevention with bezafibrate therapy for the treatment of dyslipidemia: an extended follow-up of the BIP trial.

Abstract

This study was designed to evaluate the long-term cardiovascular benefit of bezafibrate therapy in coronary heart disease patients enrolled in the BIP (Bezafibrate Infarction Prevention) trial. The BIP trial yielded a nonsignificant 7.3% reduction in the rate of major cardiac events after a mean follow-up period of 6.2 years, possibly owing to an increasing unbalanced usage of nonstudy lipid-lowering drugs (LLDs) during the course of the trial. The adjusted risk for the combined end point of cardiac death or nonfatal myocardial infarction 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 (n = 1,548) and placebo (n = 1,542) groups of the trial. During the extended follow-up period, nonstudy LLDs were administered to a significantly greater proportion of placebo-allocated patients (57%) than bezafibrate-allocated patients (53%; p = 0.02). Interaction-term analysis demonstrated that the benefit of bezafibrate therapy was pronounced (18% risk reduction; p = 0.03) without or before treatment with nonstudy LLDs initiated during follow-up and attenuated (hazard ratio 1.05; p = 0.85) after therapy with nonstudy LLDs initiated during the observation period. Consistent with these findings, treatment with bezafibrate was shown to be associated with a significant 17% risk reduction (p = 0.03) when study patients were censored from the analysis upon initiation of therapy with nonstudy LLDs. The data demonstrate that bezafibrate therapy in the BIP trial was associated with significant long-term cardiovascular protection that was attenuated by an unbalanced usage of nonstudy LLDs during the course of the trial.