INTRODUCTION The 2014 American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Rhythm Society (HRS) guidelines recommend anticoagulation to reduce clot formation and the risk of thromboembolic events in patients with atrial fibrillation but does not specify guidelines for the elderly population. Direct oral anticoagulants (DOACs) are newer US FDA-approved alternatives to warfarin and include dabigatran, rivaroxaban, apixaban and edoxaban. The efficacy of DOACs is heavily researched, but few studies have evaluated their bleeding risk. OBJECTIVES This systematic review and meta-analysis investigates which DOAC has the lowest bleeding risk in elderly patients with nonvalvular atrial fibrillation (NVAF). METHODS CINAHL and MEDLINE databases were searched using specific keywords, and 244 results were identified and screened. Inclusion criteria required a major bleeding event requiring hospitalization as an outcome and excluded patients with severe renal failure. Articles that met inclusion criteria were assessed for risk of bias using the Cochrane Tool to Assess Risk of Bias in Cohort Studies. Review Manager (version 5) was used to perform the random-effects model meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. P < 0.05 was considered statistically significant. RESULTS Six articles met inclusion criteria and encompassed 446,042 patients in total. Apixaban and dabigatran had statistically significant risk reductions compared with warfarin, whereas rivaroxaban did not (HR 0.60 [95% CI 0.52-0.69], p < 0.00001; HR 0.79 [95% CI 0.70-0.90], p = 0.0005; HR 1.03 [95% CI 0.86-1.22], p = 0.77, respectively.) Data regarding edoxaban were limited and thus not included in the analysis. CONCLUSION Apixaban and dabigatran have a significantly decreased major bleeding risk (40 and 21%, respectively) compared with warfarin. There was no statistical difference in bleeding risk between rivaroxaban and warfarin. Head-to-head prospective randomized controlled trials are required to assess the true bleeding risk of each DOAC.

中文翻译：

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非瓣膜性心房颤动直接口服抗凝药的老年人出血风险：队列研究的系统评价和荟萃分析。

引言2014年美国心脏协会（AHA）/美国心脏病学会（ACC）/心脏节律协会（HRS）指南建议抗凝以减少房颤患者的血凝块形成和血栓栓塞事件的风险，但未指定老年人指南人口。直接口服抗凝剂（DOAC）是美国FDA批准的较新的华法林替代品，包括达比加群，利伐沙班，阿哌沙班和依多沙班。对DOAC的功效进行了深入研究，但很少有研究评估其出血风险。目的这项系统的回顾和荟萃分析研究了老年非瓣膜性心房颤动（NVAF）患者中哪种DOAC出血风险最低。方法使用特定的关键词搜索CINAHL和MEDLINE数据库，并鉴定和筛选244个结果。纳入标准要求发生重大出血事件，因此需要住院治疗，并排除患有严重肾衰竭的患者。在队列研究中使用Cochrane工具评估偏倚风险，评估符合纳入标准的文章的偏倚风险。评论管理器（版本5）用于执行随机效应模型的荟萃分析。计算危害比（HRs）和95％置信区间（CIs）。P <0.05被认为具有统计学意义。结果6篇符合入选标准的文章共纳入446,042例患者。与华法林相比，阿哌沙班和达比加群的风险降低具有统计学意义，而利伐沙班则没有（HR 0.60 [95％CI 0.52-0.69]，p <0.00001； HR 0.79 [95％CI 0.70-0.90]，p = 0.0005； HR 1.03 [ 95％CI [0.86-1.22]，p = 0.77。）有关edoxaban的数据有限，因此未包含在分析中。结论与华法林相比，阿哌沙班和达比加群的主要出血风险显着降低（分别为40％和21％）。利伐沙班与华法林之间的出血风险无统计学差异。需要进行头对头前瞻性随机对照试验来评估每个DOAC的真实出血风险。