Aguilar M I, Hart R
Cochrane Database Syst Rev. 2005 Jul 20;2005(3):CD001927. doi: 10.1002/14651858.CD001927.pub2.
Non-valvular atrial fibrillation (AF) is associated with an increased risk of stroke mediated by embolism of stasis-precipitated thrombi from the left atrial appendage.
The objective is to characterize the efficacy and safety of oral anticoagulants (OACs) for the primary prevention of stroke in patients with chronic AF.
We searched the Cochrane Stroke Group Trials Register (last searched in June 2004). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2004), MEDLINE (1966 to June 2004), and the reference lists of recent review articles. We also contacted the Atrial Fibrillation Collaboration and experts working in the field to identify unpublished and ongoing trials.
All randomized controlled trials comparing OACs with control in patients with chronic non-valvular atrial fibrillation and no history of transient ischemic attack (TIA) or stroke.
Trials for inclusion were independently selected by two authors who also extracted each outcome and double-checked the data. The Peto method was used for combining odds ratios. All analysis were, as far as possible, intention-to-treat. Since the published results of four trials included 3% to 8% of participants with prior stroke or TIA, unpublished results excluding these participants were obtained from the Atrial Fibrillation Investigators.
Of 2313 participants without prior cerebral ischemia from five randomized trials, the mean age was 69 years. Participant features and study quality were similar between trials: the OAC in all five trials was warfarin. About half of participants (n = 1154) were randomized to adjusted-dose warfarin with mean achieved INRs ranging between 2.0 to 2.6. During 1.5 years mean follow up, warfarin was associated with large, highly statistically significant reductions in all strokes (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.26 to 0.59), ischemic stroke (OR 0.34, 95% CI 0.23 to 0.52), all disabling or fatal stroke (OR 0.47, 95% CI 0.28 to 0.80), death (OR 0.69, 95% CI 0.50 to 0.94) and the combined endpoint of all stroke, myocardial infarction or vascular death (OR 0.56, 95% CI 0.42 to 0.76). The observed rates of intracranial and extracranial hemorrhage were not significantly increased by OAC therapy, but the confidence intervals were wide.
AUTHORS' CONCLUSIONS: Treatment with adjusted-dose warfarin to achieved INRs of 2 to 3 reduces stroke, disabling or fatal stroke, and death for patients with non-valvular AF. The benefits were not substantially offset by increased bleeding among these participants in randomized clinical trials. Limitations include relatively short follow up and imprecise estimates of bleeding risks from the selected participants enrolled in the trials. For primary prevention of stroke in AF patients, about 25 strokes and about 12 disabling or fatal strokes would be prevented yearly for every 1000 atrial fibrillation patients given OACs.
非瓣膜性心房颤动（房颤）与左心耳淤滞沉淀血栓栓塞介导的中风风险增加有关。
本研究旨在描述口服抗凝药（OACs）对慢性房颤患者中风一级预防的疗效和安全性。
我们检索了Cochrane中风组试验注册库（最近一次检索时间为2004年6月）。此外，我们还检索了Cochrane对照试验中央注册库（CENTRAL）（《Cochrane图书馆》，2004年第4期）、MEDLINE（1966年至2004年6月）以及近期综述文章的参考文献列表。我们还联系了房颤协作组和该领域的专家，以确定未发表和正在进行的试验。
所有比较OACs与对照组治疗慢性非瓣膜性房颤且无短暂性脑缺血发作（TIA）或中风病史患者的随机对照试验。
两名作者独立选择纳入试验，并提取每个结果并对数据进行二次核对。采用Peto法合并比值比。所有分析尽可能采用意向性分析。由于四项试验的已发表结果纳入了3%至8%既往有中风或TIA的参与者，因此从房颤研究人员处获得了排除这些参与者的未发表结果。
五项随机试验中2313名无既往脑缺血的参与者，平均年龄为69岁。各试验间参与者特征和研究质量相似：所有五项试验中的OAC均为华法林。约一半参与者（n = 1154）被随机分配至调整剂量华法林组，平均国际标准化比值（INRs）在2.0至2.6之间。在平均1.5年的随访期间，华法林与所有中风（比值比（OR）0.39，95%置信区间（CI）0.26至0.59）、缺血性中风（OR = 0.34，95% CI 0.23至0.52）、所有致残或致命性中风（OR 0.47，95% CI 0.28至0.80）、死亡（OR 0.69，95% CI 0.50至0.94）以及所有中风、心肌梗死或血管性死亡的联合终点（OR 0.56，95% CI 0.42至0.76）的大幅、高度统计学显著降低相关。OAC治疗未显著增加颅内和颅外出血的观察发生率，但置信区间较宽。
调整剂量华法林治疗使INRs达到2至3可降低非瓣膜性房颤患者的中风、致残或致命性中风以及死亡风险。在随机临床试验中，这些参与者出血增加并未显著抵消获益。局限性包括随访时间相对较短以及对试验中所选参与者出血风险的估计不精确。对于房颤患者中风的一级预防，每1000名接受OACs治疗的房颤患者每年可预防约25次中风和约12次致残或致命性中风。
