Archontakis-Barakakis Paraschos, Kokkinidis Damianos G, Nagraj Sanjana, Gidwani Vipul, Mavridis Theodoros, Ntaios George
Northeast Internal Medicine Associates, LaGrange, IN 46845, USA.
Section of Cardiovascular Medicine, Yale University School of Medicine, Yale New Haven Hospital, New Haven, CT 06510, USA.
Rev Cardiovasc Med. 2022 Oct 10;23(10):334. doi: 10.31083/j.rcm2310334. eCollection 2022 Oct.
Real-world, observational studies have investigated the safety profile of Direct Oral Anticoagulants (DOACs) on Major Hemorrhage (MH) used for stroke prevention in Non-Valvular Atrial Fibrillation (NVAF). We performed a systematic review and meta-analysis to investigate the comparative safety of DOACs versus other DOACs and versus Vitamin K Antagonists (VKAs) adhering to PRISMA guidelines. We defined MH according to the International Society on Thrombosis and Haemostasis statement or as the composite outcome of intracranial, gastrointestinal, genitourinary, respiratory, cavitary and musculoskeletal bleeding in case of studies using International Statistical Classification of Diseases codes for patient selection.
We systematically investigated two databases (Medline, Embase) until April of 2021, gathered observational studies and extracted hazard ratios (HRs) with 95% confidence intervals (CI) on our outcome of interest. Additional subgroup analyses according to DOAC dosing, prior diagnosis of chronic kidney disease, prior diagnosis of stroke, history of previous use of VKA, the users' age, the users' gender and study population geographic region were conducted. All analyses were performed with a random-effects model.
From this search, 55 studies were included and 76 comparisons were performed. The MH risk associated with Rivaroxaban use was higher than the risk with Dabigatran use (HR: 1.32, 95% CI: 1.21-1.45, : 12.39%) but similar to VKA use (HR: 0.94, 95% CI: 0.87-1.02, : 76.57%). The MH risk associated with Dabigatran use was lower than the risk with VKA use (HR: 0.75, 95% CI: 0.64-0.90, : 87.57%). The MH risk associated with Apixaban use was lower than the risk with Dabigatran use (HR: 0.75, 95% CI: 0.64-0.88, : 58.66%), with Rivaroxaban use (HR: 0.58, 95% CI: 0.50-0.68, : 74.16%) and with VKA use (HR: 0.60, 95% CI: 0.55-0.65, : 58.83%). Our aforementioned subgroup analyses revealed similar results.
All in all, Apixaban was associated with a reduced MH risk compared to Dabigatran, Rivaroxaban and VKA. Dabigatran was associated with a reduced MH risk compared to both Rivaroxaban and VKA.
真实世界的观察性研究调查了直接口服抗凝剂（DOACs）用于非瓣膜性心房颤动（NVAF）患者预防卒中时发生大出血（MH）的安全性。我们按照PRISMA指南进行了一项系统评价和荟萃分析，以研究DOACs与其他DOACs以及与维生素K拮抗剂（VKAs）相比的相对安全性。我们根据国际血栓与止血学会的声明定义大出血，或者在使用国际疾病分类代码进行患者选择的研究中，将大出血定义为颅内、胃肠道、泌尿生殖系统、呼吸道、空洞性及肌肉骨骼出血的复合结局。
我们系统检索了两个数据库（Medline、Embase）至2021年4月，收集观察性研究，并提取了我们感兴趣结局的风险比（HRs）及95%置信区间（CI）。根据DOAC剂量、慢性肾脏病既往诊断、卒中既往诊断、VKA既往使用史、使用者年龄、使用者性别及研究人群地理区域进行了额外的亚组分析。所有分析均采用随机效应模型。
通过此次检索，纳入了55项研究并进行了76项比较。与使用利伐沙班相关的大出血风险高于使用达比加群的风险（HR：1.32，95%CI：1.21 - 1.45，P值：12.39%），但与使用VKA相似（HR：0.94，95%CI：0.87 - 1.02，P值：76.57%）。与使用达比加群相关的大出血风险低于使用VKA的风险（HR：0.75，95%CI：0.64 - 0.90，P值：87.57%）。与使用阿哌沙班相关的大出血风险低于使用达比加群的风险（HR：0.75，95%CI：0.64 - 0.88，P值：58.66%）、低于使用利伐沙班的风险（HR：0.58，95%CI：0.50 - 0.68，P值：74.16%）以及低于使用VKA的风险（HR：0.60，95%CI：0.55 - 0.65，P值：58.83%）。我们上述的亚组分析显示了相似的结果。
总体而言，与达比加群、利伐沙班和VKA相比，阿哌沙班与大出血风险降低相关。与利伐沙班和VKA相比，达比加群与大出血风险降低相关。
