Treatment with bezafibrate is associated with reduced risk of cancer in patients with coronary heart disease

Background: Bezafibrate, peroxisome proliferator activator receptor a (PPARa) agonist, appears to downregulate vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR) and hypoxia inducible factor-1 a (HIF-1a) and thus may have adjunct role for the treatment of cancer.

Objective: This study was designed to evaluate the possible long-term reduction in cancer risk associated with bezafibrate therapy among participants with coronary heart disease (CHD).

Methods: Participants were 2980 patients with CHD (mean age, 60.0 years; 92% men), free of cancer, enrolled in the Bezafibrate Infarction Prevention (BIP), a double-blind trial, from 1990-1992. Patients randomized to receive 400 mg of bezafibrate (n=1486) or a placebo (n=1494) daily were followed up for cancer for a median of 21.3 years. Survival techniques were used to assess the bezafibrate-cancer association.

Results: Clinical characteristics and laboratory values were well balanced between the two groups. During 46108 person-years of follow-up, 753 patients developed cancer. With death considered a competing event, the cumulative incidence of cancer was lower in the bezafibrate vs placebo groups, with the lines diverging at approximately 2 years (Figure). The overall hazard ratio (95% CI) for cancer in in the bezafibrate vs placebo groups was 0.85 (0.74-0.98). The association was not sensitive to adjustment for on-trial lipid levels, but was attenuated (hazard ratio, 0.92; 95% CI: 0.79-1.07) upon adjustment for on-trial fibrinogen levels.

Conclusions: Bezafibrate treatment is associated with reduced risk of cancer among CHD patients enrolled in the BIP trial. The association is partially mediated through on-trial fibrinogen but not lipid levels.