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 significant 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 benefit 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.