Berger Jeffrey S, Bhatt Deepak L, Cannon Christopher P, Chen Zhengming, Jiang Lixin, Jones James B, Mehta Shamir R, Sabatine Marc S, Steinhubl Steven R, Topol Eric J, Berger Peter B
New York University School of Medicine, New York, New York, USA.
J Am Coll Cardiol. 2009 Nov 17;54(21):1935-45. doi: 10.1016/j.jacc.2009.05.074.
This study sought to investigate the efficacy and safety of clopidogrel in women and men.
Previous analyses have shown sex-based differences in response to several antiplatelet medications. Little is known about the efficacy and safety of clopidogrel in women and men.
This study performed a meta-analysis of all blinded randomized clinical trials comparing clopidogrel and placebo (CURE [Clopidogrel in Unstable Angina to Prevent Recurrent Events], CREDO [Clopidogrel for the Reduction of Events During Observation], CLARITY-TIMI 28 [Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infarction 28], COMMIT [Clopidogrel and Metoprolol in Myocardial Infarction Trial], and CHARISMA [Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance] trials), involving a total of 79,613 patients, of whom 30% were women. The relative efficacy and safety of clopidogrel at reducing cardiovascular events (cardiovascular death, myocardial infarction [MI], or stroke) in women and men was estimated using random-effects modeling.
Overall, clopidogrel was associated with a highly significant 14% proportional reduction in the risk of cardiovascular events (odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.80 to 0.93), with no significant differences in treatment effect between women and men. Among the 23,533 women enrolled, there were fewer cardiovascular events in the clopidogrel group compared with the placebo group (11.0% vs. 11.8%; OR: 0.93; 95% CI: 0.86 to 1.01). In women the risk reduction with clopidogrel seemed to be greatest for MI (OR: 0.81; 95% CI: 0.70 to 0.93), with the effects on stroke (OR: 0.91; 95% CI: 0.69 to 1.21) or total death (OR: 0.99; 95% CI: 0.90 to 1.08) not statistically significant. Among the 56,091 men enrolled, there were fewer cardiovascular events in those receiving clopidogrel compared with placebo (7.8% vs. 9.0%; OR: 0.84; 95% CI: 0.78 to 0.91), and the risk reduction was significant for MI (OR: 0.83; 95% CI: 0.76 to 0.92), stroke (OR: 0.83; 95% CI: 0.71 to 0.96), and total death (OR: 0.91; 95% CI: 0.84 to 0.97). Clopidogrel increased the risk of major bleeding in both women (OR: 1.43; 95% CI: 1.15 to 1.79) and men (OR: 1.22; 95% CI: 1.05 to 1.42).
Clopidogrel reduces the risk of cardiovascular events in both women and men.
本研究旨在调查氯吡格雷在女性和男性中的疗效及安全性。
既往分析显示，在对几种抗血小板药物的反应方面存在基于性别的差异。关于氯吡格雷在女性和男性中的疗效及安全性，人们了解甚少。
本研究对所有比较氯吡格雷与安慰剂的双盲随机临床试验（“CURE”[氯吡格雷用于不稳定型心绞痛预防复发事件]、“CREDO”[氯吡格雷用于降低观察期内事件发生率]、“CLARITY-TIMI 28”[氯吡格雷作为辅助再灌注治疗——心肌梗死溶栓28]、“COMMIT”[氯吡格雷与美托洛尔在心肌梗死试验中的应用]以及“CHARISMA”[氯吡格雷用于高动脉粥样硬化血栓形成风险和缺血性稳定、管理及预防]试验）进行了荟萃分析，共纳入79613例患者，其中30%为女性。采用随机效应模型估计氯吡格雷在降低女性和男性心血管事件（心血管死亡、心肌梗死[MI]或卒中）方面的相对疗效及安全性。
总体而言，氯吡格雷使心血管事件风险显著降低了14%（比值比[OR]：0.86；95%置信区间[CI]：0.80至0.93），女性和男性之间的治疗效果无显著差异。在纳入的23533例女性中，氯吡格雷组的心血管事件少于安慰剂组（11.0%对11.8%；OR：0.93；95%CI：0.86至1.01）。在女性中，氯吡格雷对心肌梗死的风险降低似乎最大（OR：0.81；95%CI：0.70至0.93），对卒中（OR：0.91；95%CI：0.69至1.21）或全因死亡（OR：0.99；95%CI：0.90至1.08）的影响无统计学意义。在纳入的56091例男性中，接受氯吡格雷治疗者的心血管事件少于接受安慰剂者（7.8%对9.0%；OR：0.84；9×CI：0.7×至0.91），对心肌梗死（OR：0.83；95%CI：0.76至0.92）、卒中（OR：0.83；95%CI：0.71至0.96）和全因死亡（OR：0.91；95%CI：0.84至0.97）的风险降低具有统计学意义。氯吡格雷增加了女性（OR：1.43；95%CI：1.15至1.79）和男性（OR：1.22；95%CI：1.05至1.42）发生大出血的风险。
氯吡格雷可降低女性和男性的心血管事件风险。
