阿司匹林单独或与氯吡格雷联合用药治疗缺血性脑卒中及短暂性脑缺血发作疗效和不良反应的Meta分析

目的 系统评价阿司匹林单独或与氯吡格雷联合用药治疗缺血性脑卒中及短暂性缺血发作的疗效,以及出血不良反应发生风险。方法 在Cochrane Library、Medline、Embase以及Web of Science数据库(1998年1月1日至2015年4月1日)中检索符合要求的随机对照试验研究,按照Cochrane风险偏倚评估工具评价纳入研究的方法学质量并提取有效数据,用随机效应模型计算合并效应及95%CI。按照不同人群、疾病亚型、治疗持续时间及有无氯吡格雷负荷剂量进行分层分析。结果 共纳入7篇符合标准的文献,包括14 022名研究对象。Meta分析显示,阿司匹林与氯吡格雷联合用药与阿司匹林单独用药组相比能降低脑卒中复发风险(RR=0.71,95%CI:0.61～0.84,P<0.001)、增高出血事件发生的风险(RR=1.60,95%CI:1.46～1.76,P<0.001)。分层分析显示,中国人群联合用药后脑卒中复发风险(RR=0.55,95%CI:0.34～0.89)低于其他人群(RR=0.78,95%CI:0.66～0.93),出血事件发生风险(RR=1.41,95%CI:1.01～1.96)低于其他人群(RR=1.62,95%CI:1.47～1.79);氯吡格雷负荷剂量组复发风险(RR=0.69,95%CI:0.58～0.81)低于没有负荷剂量的亚组(RR=0.74,95%CI:0.56～0.99),出血事件发生风险(RR=1.59,95%CI:1.10～2.30)与没有负荷剂量的亚组(RR=1.60,95%CI:1.46～1.77)相比,差别不大。结论 阿司匹林与氯吡格雷联合用药相比阿司匹林单独用药能够降低缺血性脑卒中及短暂性脑缺血发作患者的复发风险,但同时也会增加患者出血的风险。在中国人群中,阿司匹林与氯吡格雷联合用药比阿司匹林单独用药对于减少脑卒中复发的效果更好且不增加患者出血的风险。

Meta-analysis on the efficacy and adverse events of aspirin plus clopidogrel versus aspirin-mono-therapy in patients with ischemic stroke or transient ischemic attack

Objective To present the systematic assessment on the efficacy and bleeding adverse events of dual-antiplatelet therapy with aspirin and clopidogrel versus aspirin-mono-antiplatelet therapy in patients with ischemic stroke or transient ischemic attack. Methods Retrieve randomized controlled trials conformed to the inclusion and exclusion criteria in Cochrane Library, Medline, Embase, and Web of Science electronic database, between January 1, 1998 and April 1, 2015. Cochrane Collaboration was used to assess the methodological quality of the included research papers. Stratification analysis was performed on factors as: race, subtypes of the disease, duration of follow-up and with or without clopidogrel loading dose, of the patients. Results A total of 7 studies were eligible for analysis, including 14 022 study objects. Data from Meta-analysis showed that dual-antiplatelet therapy, when compared to the mono-therapy group, could reduce the risk of recurrent stroke(RR=0.71, 95%CI:0.61-0.84,P<0.001), at the same time, increase the risk of bleeding events(RR=1.60,95%CI:1.46-1.76,P<0.001). Data derived from the Hierarchical analysis showed that the risk of stroke recurrence in Chinese population (RR=0.55, 95%CI: 0.34-0.89) was lower than recorded in other populations (RR=0.78, 95%CI: 0.66-0.93), with the risks of bleeding events as RR=1.41(95%CI: 1.01-1.96) and RR=1.62(95%CI:1.47-1.79), respectively. Risk of recurrence among the group with clopidogrel loading dose (RR=0.69,95%CI:0.58-0.81) was less than those without (RR=0.74, 95%CI:0.56-0.99). The risks of occurrence on bleeding events were RR=1.59(95%CI:1.10-2.30) and RR=1.60(95%CI:1.46-1.77), respectively. Conclusion The combined therapy of aspirin and clopidogrel could reduce the risk of recurrence of ischemic stroke and TIA patients, but increase the risk of bleeding, when compared to the group that using aspirin alone for the therapy. In Chinese population, the combined therapy seemed more effective than using aspirin alone in reducing the recurrence of stroke, but without increasing the risk of bleeding.