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 (< or =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).


CONCLUSIONS
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.
Goldenberg
Ilan
I
Heart Institute, Sheba Medical Center, Tel-Hashomer, Israel.
Boyko
Valentina
V
Tennenbaum
Alexander
A
Tanne
David
D
Behar
Solomon
S
Guetta
Victor
V
D000368:Aged; D001629:Bezafibrate / Q000627:therapeutic use*; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy / Q000401:mortality* / Q000517:prevention & control; D013997:Time Factors; D016896:Treatment Outcome
D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D001629:Bezafibrate