抗血小板与抗凝治疗预防非瓣膜性心房颤动缺血性卒中的疗效评价

A meta-analysis on efficacy of anti-platelet agents and anticoagulants for preventing stroke in patientswith nonvalvular atrial fibrillation

目的评价抗血小板治疗与抗凝治疗预防非瓣膜性心房颤动（房颤）缺血性卒中疗效及安全性。方法采用Cochrane系统评价方法，计算机检索PubMed、EMbase、CENTREN及其下属各临床注册试验数据中心、中国生物医学文献数据库、中文科技期刊数据库、中国期刊全文数据库，检索时间截至2009年12月，纳人中外文抗血小板治疗与抗凝治疗预防非瓣膜性房颤缺血性卒中随机对照试验（RCT）。由两名评价者独立评价纳入研究质量、提取资料并交叉核对。采用RevMan5．0软件进行荟萃分析。结果共纳入14个RCT，包括15880例患者。荟萃分析结果显示：与对照组比较，抗血小板治疗不减少非瓣膜性房颤缺血性卒中（RR=0．83，95％C10．68～1．00，P=0．05），不减少房颤全因死亡（RR=0．88，95％C10．73～1．07，P=0．21），可能增加房颤患者严重出血1．9倍（RR=2．88，95％CI1．21～6．86，P=0．02），不减少房颤体循环栓塞（RR=0．71，95％C10．34-1．51，P=0．38），不增加房颤患者颅内出血（RR=3．25，95％C10．84～12．62，P=0．09）。抗血小板治疗与抗凝治疗比较显示：抗凝治疗显著降低房颤缺血性卒中发生率（RR=1．84，95％C11．48～2．28，P〈0．01），房颤全因病死率二者差异无统计学意义（RR=1．06，95％C10．90-1．23，P=0．50），严重出血发生率二者差异无统计学意义（RR=0．95，95％C10．76～1．19，P=0．66），抗凝治疗显著降低房颤体循环栓塞发生率（RR=1．94，95％CI1．24～3．03，P=0．004），抗凝治疗显著增加颅内出血发生率（RR=0．49，95％C10．31～0．78，P=0．003）。结论与对照组比较，抗血小板治疗不减少非瓣膜性房颤缺血性卒中及体循环栓塞，并可能增加房颤严重出血事件1．9倍；抗血小板治疗与抗凝治疗比较，抗凝治疗显著降低房颤缺血性卒中及体循环栓塞发生率，不增加房颤严重出血但显著增加颅内出血发生率。由于纳入的研究有限，结局指标不够统一，得出的结论尚需更多设计严谨、使用统一结局指标、随访时间较长的大样本RCT来进一步证实。

Objective To evaluate the efficacy and security of anti-platelet and anticoagulant therapy on prevention of ischemic stroke in patients with nonvalvular atrial fibrillation （ NAF）. Methods We searched PubMed,EMbase,CENTREN and its affiliated clinical trial registration data center, CBMdisc, VIP,and CNKI databases from establishment to Dec 2009 to identify randomized controlled trials （RCTs） covering the use of anti-platelet agents and anticoagulants for patients with NAF. Meta-analysis was performed by using RevMan 5.0 software after the strict evaluation of the methodological quality of the included RCTs. Results Fourteen RCTs involving 15 880 patients were include. Compared with placebo or no use of anti-platelet drugs, antiplatelet therapy didn＇t reduce ischemic stroke （RR = 0. 83,95% CI O. 68 tol. 00, P= 0.05）, systemic emboli （RR =0.71, 95%CI0.34 to 1.51, P= 0.38） and all-cause mortality （RR = 0. 88, 95% CI O. 73 to 1.07, P = 0. 21 ） while significantly increased the major bleeding （RR = 2. 88, 95% CI 1.21 to 6. 86, P = 0. 02） in patients with NAF, intracranial hemorrhage was not affected by antiplatelet therapy in patients with atrial fibrillation （RR = 3.25, 95% CI O. 84 to 12. 62, P =0. 09）. Compared with anti-platelet therapy, anticoagulant therapy significantly reduced the incidence of ischemic stroke （RR = 1.84,95% CI 1.48 to 2. 28,P〈0. 01） and systemic emboli （RR = 1.94, 95% CI 1.24 to 3.03, P = 0. 004 ） but significantly increased the incidence of intracranial hemorrhage （ RR = 0.49, 95% CIO. 31 to 0. 78, P = 0. 003）, did not affect all-cause mortality （RR = 1.06, 95% CIO. 90 to 1.23, P = 0. 50） and the incidence of major bleeding （RR = 0. 95, 95% CIO. 76 to 1.19, P = 0. 66） in NAF patients. Conclusions Compared with the placebo and no use of anti-platelet drugs, anti-platelet therapy didn＇t reduce ischemic stroke and systemic emboli but increased the risk of major bleeding in NAF patients. Compared with anti-platelet therapy, anticoagulant therapy significantly reduced the ischemic stroke and systemic emboli without increasing the risk of major bleeding, but significantly increased the incidence of intracranial hemorrhage in NAF patients. Since the study included RCTs with limited and less uniform outcome endpoints, the conclusions should be verified with RCTs with more uniform endpoints and longer follow-up time.