Lower on-treatment low-density lipoprotein cholesterol and major adverse cardiovascular events in women and men: pooled analysis of 10 ODYSSEY phase 3 alirocumab trials

Background- — In statin trials, men and women derived similar relative risk reductions in cardiovascular events per 39 mg/dL low- density lipoprotein cholesterol (LDL-C) reduction. We explored whether lower LDL-C levels and greater LDL-C percentage reductions than those achieved with statins are associated with reduced major adverse cardiovascular event (MACE) rates in women as well as men. Methods and Results- — Data pooled from 10 phase 3 ODYSSEY randomized trials (n = 4983) comparing alirocumab with control (placebo/ezetimibe) were assessed for association between 39 mg/dL lower on-treatment LDL-C and percentage LDL-C change from baseline, and MACE risk by sex, using multivariable Cox regression. Mean baseline LDL-C was 135 mg/dL (women) and 121 mg/dL (men). Average on-treatment LDL-C levels with alirocumab, ezetimibe, and placebo were 71, 114, and 134 mg/dL, respectively, in women (n = 1882) and 52, 93, and 122 mg/dL, respectively, in men (n = 3090). Overall, 36.5% and 58.7% of women and men, respectively, achieved on-treatment LDL-C < 50 mg/dL. Each 39 mg/dL lower LDL-C was associated with a 33% and 22% lower risk of MACE in women ( P = 0.0209) and men ( P = 0.0307), respectively, with no signi fi cant between-sex difference ( P for heterogeneity = 0.4597). Results were similar when analyzed per 50% LDL-C reduction, 24% ( P = 0.1094) and 29% ( P = 0.0125) lower MACE risk in women and men, respectively ( P for heterogeneity = 0.7499). Alirocumab was generally well tolerated in both sexes. Conclusions- — The present analysis reinforces the notion that both sexes derive a similar cardiovascular bene fi t from LDL-C lowering. Although women had slightly higher on-treatment LDL-C than men, both sexes showed a similar lower MACE risk with lower LDL-C