Long-term Benefit of High-Density Lipoprotein Cholesterol–Raising Therapy With Bezafibrate: 16-Year Mortality Follow-up of the Bezafibrate Infarction Prevention Trial

Background Major randomized trials of fibrate therapy demonstrate an inverse relationship between on-treatment high-density lipoprotein cholesterol (HDL-C) increments and clinical outcome. We hypothesized that the degree of HDL-C response to bezafibrate is independently associated with subsequent long-term mortality. Methods The risk of death at 16 years of follow-up among 3026 patients with coronary heart disease allocated to the original bezafibrate (n = 1509) and placebo (n = 1517) arms of the Bezafibrate Infarction Prevention (BIP) trial was related to HDL-C response to bezafibrate therapy, categorized as upper-tertile (>8 mg/dL) or lower-tertile (≤8 mg/dL) on-treatment HDL-C change. Results Multivariate analysis demonstrated that patients allocated to bezafibrate therapy experienced a significant 11% reduction ( P  = .06) in the risk of long-term mortality compared with placebo-allocated patients. Mortality reduction among bezafibrate-allocated patients was related to a significant 22% ( P  = .008) reduction in the risk of death in patients with an upper-tertile HDL-C response to therapy, whereas among patients with a lower HDL-C response, the risk of death was similar to that of the placebo group (hazard ratio, 0.95; P  = .43). Accordingly, the cumulative probability of death at 16 years was significantly lower among bezafibrate-allocated patients with an upper-tertile HDL-C response (32.1%) compared with the placebo group (37.9%; P  = .02), whereas patients with a lower HDL-C response to treatment displayed a mortality rate (36.8%) similar to the placebo group ( P  = .57). Conclusion Our findings suggest that HDL-C level–raising therapy with bezafibrate is associated with long-term mortality reduction that may be related to the degree of HDL-C response to treatment.