摘要： 目的 评价达比加群在脑卒中二级预防中的适用范围、疗效和安全性。方法 分别以dabigatran、stroke、ischemia、hemorrhagic、TIA、transient ischemic attack、prevention、secondary prevention、treatment 等英文词组为检索词，检索2005 年1 月-2015 年1 月美国国立医学图书馆，ScienceDirect 数据库，英国Cochrane 图书馆，并辅助手工检索获得临床指南、系统评价（包括Meta 分析）、随机对照试验、回顾性病例分析、病例观察研究和综述等相关文献，采用Jadad 量表评价临床研究、PRISMA 评价清单考察系统评价（包括Meta 分析）和综述质量。结果经筛选最终获得有关达比加群用于脑卒中二级预防的英文文献23 篇，临床指南2 篇、系统评价（包括Meta 分析）和综述6 篇、随机对照试验8 篇、回顾性病例分析3 篇、病例观察研究4 篇；临床研究高质量文献8 篇、低质量7 篇，系统评价（包括Meta 分析）和综述均为高质量文献。结果 显示：（1）达比加群用于非瓣膜性心房颤动患者的脑卒中二级预防，尤其是亚洲患者，具有不低于华法林的疗效和高于华法林的安全性，高龄患者宜采用小剂量，并且可能需要监测血药浓度。（2）达比加群用于心脏机械瓣膜置换术后的脑卒中二级预防应慎重，目前有不充分的证据显示其疗效和安全性并未优于华法林。（3）达比加群用于心脏瓣膜病、心肌病、心肌梗死及其他需抗凝治疗疾病的脑卒中二级预防尚缺乏循证证据，其疗效和安全性尚待大规模临床试验证实。（4）达比加群是否能够常规用于脑卒中二级预防尚待进一步研究。结论 循证医学方法对评价达比加群在脑卒中二级预防中的应用具有重要意义。达比加群用于脑卒中二级预防应慎重。

关键词: 卒中, 抗凝药, 循证医学

Abstract: Objective  To evaluate the efficiency, safety and indications of dabigatran for the secondary prevention of stroke.  Methods  Taking dabigatran, stroke, ischemia, hemorrhagic, TIA, transient ischemic attack, prevention, secondary prevention, treatment as search terms, retrieve in databases such as PubMed, ScienceDirect and Cochrane Library, assisted by manual searching, in order to collect relevant literatures including clinical guidelines, systematic reviews (including Meta-analyses), randomized controlled trials (RCTs), retrospective case analyses, case-observation studies and reviews. Jadad Scale was applied for scoring clinical researches while PRISMA statement was for evaluating the quality of systematic reviews (including Meta-analyses) and reviews.  Results  A total of 23 articles were selected out of 1067 search results, in which 2 clinical guidelines, 6 systematic reviews (including Meta-analyses) and reviews, 8 RCTs, 3 retrospective case analyses, and 4 case-observation studies were enrolled. According to the Jadad Scale, 8 clinical studies were evaluated as high-quality literature (score ≥ 4), and the remaining 7 were low-quality literature (score < 4). All of systematic reviews (including Meta-analyses) and reviews were of high quality. The results were as follows: 1) the use of dabigatran in stroke patients, especially Asian patients, with non-valvular atrial fibrillation showed no inferior efficiency and lower risk for major bleeding for the secondary prevention of stroke than warfarin, while the elder should be given lower dosage and blood concentration of drug might be in need of monitoring. 2) Applying dabigatran for the secondary prevention of stroke in patients with mechanical valve replacement must be cautious. Insufficient evidence had shown its inferiority in both efficiency and safety when compared to warfarin. 3) Large-scale clinical trials are needed to provide evidence for the application of dabigatran in valvular heart disease, cardiomyopathy, myocardial infarction, and other diseases in need of anticoagulants for secondary prevention of stroke. 4) Current evidence is limited for the regular usage of dabigatran for secondary prevention of stroke.  Conclusions  Critical findings have been demonstrated in the evidence-based evaluation on dabigatran in the secondary prevention of stroke. Decision making on the clinical application of dabigatran in the secondary prevention of stroke should be cautious.

Key words: Stroke, Anticoagulants, Evidence-based medicine