阿司匹林联合氯吡格雷治疗进展性脑卒中有效性和安全性的Meta分析

Efficacy and Safety of Aspirin Combined with Clopidogrel in the Treatment of Progressing Stroke:A Meta-analysis

目的:系统评价阿司匹林联合氯吡格雷治疗进展性脑卒中的有效性和安全性。方法:计算机检索Cochrane图书馆、PubMed、Embase、Clinical trials.gov、中国生物医学文献数据库、维普中文科技期刊数据库、万方数据库和中国知网等,收集阿司匹林联合氯吡格雷双重抗血小板(以下简称"双抗",试验组)对比阿司匹林或氯吡格雷单用抗血小板(以下简称"单抗",对照组)治疗进展性脑卒中的随机对照试验(RCT)。筛选文献、提取资料后采用Cochrane系统评价员手册5.2推荐的偏倚风险评估工具评价文献质量,采用Rev Man 5.3软件进行Meta分析。结果:共纳入27项RCT,共计2 854例患者。Meta分析结果显示,试验组患者有效率显著高于阿司匹林单抗组[RR=1.31,95%CI(1.26,1.37),P<0.000 01],神经功能缺损(NDS)评分显著低于对照组[MD=-3.80,95%CI(-5.30,-2.30),P<0.000 01],美国国立卫生研究院脑卒中量表评分显著低于阿司匹林单抗组[MD=-3.72,95%CI(-5.25,-2.20),P<0.000 01]及氯吡格雷单抗组[MD=-2.44,95%CI(-4.14,-0.73),P=0.005];亚组分析结果显示,试验组患者治疗14 d后[MD=-2.19,95%CI(-3.11,-1.27),P<0.000 01]、治疗15 d后[MD=-5.73,95%CI(-10.65,-0.81),P=0.02]、治疗28 d后[MD=-3.45,95%CI(-4.24,-2.67),P<0.000 01]NDS评分均显著低于对照组。试验组与氯吡格雷单抗组患者有效率、与阿司匹林单抗组及氯吡格雷单抗组不良反应发生率、与阿司匹林单抗组及氯吡格雷单抗组出血事件发生率、与对照组患者死亡率比较差异均无统计学意义(P>0.05)。结论:阿司匹林联合氯吡格雷双抗治疗进展性脑卒中,在短期内可提高患者疗效,改善其神经功能缺损症状,但不能降低治疗期间的不良反应发生风险及死亡率。

OBJECTIVE: To systematically evaluate the efficacy and safety of aspirin combined with clopidogrel in the treatment of progressing stroke. METHODS:Retrieved from the Cochrane library,Pub Med,Embase,Clinical trials.gov,CBM,VIP,Wanfang database and CNKI databases,randomized controlled trials(RCTs)about aspirin combined with clopidogrel(trial group) versus aspirin or clopidogrel alone(control group) in the treatment of progressing stroke were collected. After literature screening and data extraction,the quality of literatures were evaluated with bias risk assessment tool recommended by Cochrane system evaluator manual 5.2. Meta-analysis was performed by using Rev Man 5.3 software. RESULTS:A total of 27 RCTs involving 2 854 patients were enrolled. The results of Meta-analysis showed that response rate of trial group was significantly higher than aspirin group [RR=1.31,95%CI(1.26,1.37),P<0.000 01];Neurological deficit score(NDS)of trial group was significantly lower than control group [MD=-3.80,95%CI(-5.30,-2.30),P<0.000 01];National Institutes of Health Stroke Scale Score in trial group was significantly lower than aspirin group [MD=-3.72,95% CI(-5.25,-2.20),P<0.000 01] and clopidogrel group[MD=-2.44,95% CI(-4.14,-0.73),P=0.005]. Results of subgroup analysis showed that NDS score of trial group was significantly lower than control group after 14 d of treatment [MD=-2.19,95%CI(-3.11,-1.27),P<0.000 01],15 d of treatment[MD=-5.73,95%CI(-10.65,-0.81),P=0.02] and 28 d of treatment [MD=-3.45,95%CI(-4.24,-2.67),P<0.000 01].Compared with trial group,there was no statistical significance in response rate with clopidogrel group,the incidence of ADR with clopidogrel group, the incidence of bleeding event with clopidogrel group, and mortality with control group(P>0.05).CONCLUSIONS:Aspirin combined with clopidogrel in the treatment of progressive stroke,can improve the efficacy and improve neurological deficit symptoms in the short term,but can not reduce the incidence of ADR or the mortality during the treatment.