Abstract 2220: The Relative Safety and Efficacy of Clopidogrel in Women and Men: Meta-Analysis of 79,613 Patients Enrolled in CREDO, CURE, CLARITY-TIMI 28, COMMIT, and CHARISMA
Background: Previous analyses have demonstrated sex-based differences in the efficacy of several anti-platelet medications. Little is known about the safety and efficacy of clopidogrel in women and men.
Methods: We performed a meta-analysis of all blinded randomized clinical trials comparing clopidogrel and placebo (CREDO, CURE, CLARITY-TIMI 28, COMMIT, and CHARISMA). The relative safety and efficacy of clopidogrel at reducing cardiovascular events (death, MI or stroke) in women and men was estimated using random-effects modeling.
Results: In all 79,613 patients, there was a reduction of cardiovascular events with clopidogrel vs placebo (9.7% vs 8.7%; OR 0.88 [0.84–0.93], P<0.01). Among the 23,522 women enrolled, there were 1289/11757 (11.0%) cardiovascular events in the clopidogrel group vs. 1372/11766 (11.7%) in the placebo group (OR 0.93 [0.86–1.01], P=0.09). Clopidogrel had its greatest effect in reducing the risk of MI (OR 0.82 [0.70–0.95], P=0.01) in women. No significant reduction was noted for stroke (OR 0.91 [0.67–1.24], P=0.56) or death (OR 0.99 [0.90–1.08], P=0.78). Among the 56,091 men enrolled, there were 2166/28064 (7.7%) cardiovascular events in the clopidogrel group vs 2492/28027 (8.9%) in the placebo group (OR 0.85 [0.79–0.91], P<0.01). Clopidogrel significantly reduced the risk of MI (OR 0.84 [0.76–0.92], P<0.01), stroke (OR 0.83 [0.71–0.96], P=0.01), and death (OR 0.91 [0.84–0.98], P<0.01). Clopidogrel increased the risk of major bleeding in both women (1.6% vs 1.1%, OR 1.43 [1.14–1.79]) and men (1.2% vs 1.0%, OR 1.21 [1.03–1.42]). The safety and efficacy were similar in patients with an acute coronary syndrome and established cardiovascular disease. There was no evidence of statistical heterogeneity (as measured by the Q-test and I2) in pooled analyses comparing women and men for the composite endpoint, its individual components, or bleeding.
Conclusions: Clopidogrel reduces the risk of cardiovascular events in both women and men. While the directionality and proportionality of the reductions are roughly similar, the effect was driven by a reduction of MI in women. The reduction of MI, stroke and death by clopidogrel in men were all significant. Clopidogrel increased the risk of major bleeding by 43% in women and 21% in men.