Zhou Ya, Yao Zhihao, Zhu Linjie, Tang Yong, Chen Jie, Wu Jianming
School of Pharmacy, Southwest Medical University, Luzhou, China.
Affiliated Hospital of Stomatology, Southwest Medical University, Luzhou, China.
Front Pharmacol. 2021 Feb 2;12:626063. doi: 10.3389/fphar.2021.626063. eCollection 2021.
Dabigatran is a univalent low-molecular-weight direct thrombin inhibitor which was developed as an alternative to vitamin K antagonists (VKAs). However, the safety of dabigatran remains controversial so far. In this study, we aimed to compare the risk of bleeding, fatal adverse events, and the all-cause mortality of dabigatran with those of the control group by a systematic review and meta-analysis of randomized controlled trials. We systematically searched PubMed, Web of Science, Cochrane Library, Medline, Embase, Wanfang database, Clinical trial, China National Knowledge Infrastructure Chinese Scientific Journal database (VIP), and Chinese Biological Medicine database (CBM), for clinical trials on conventional treatments compared with dabigatran, published between January 2014 and July 2020. The reported outcomes, including the endpoints of primary safety, were systematically investigated. Seven RCTs ( = 10,743) were included in the present systematic review. Compared to the control groups, dabigatran was not associated with an increased risk of major bleeding (relative risk [RR] 0.86, 95% confidence interval [CI]: 0.61 to 1.21, = 0.06), intracranial hemorrhage (RR 0.89, 95% CI: 0.58 to 1.36, = 0.41), fatal adverse reactions (RR 0.87, 95% CI: 0.65 to 1.17, = 0.66), all-cause mortality (RR 0.88, 95% CI: 0.70 to 1.11, = 0.45, I = 0%), and significantly reduced risk of clinically relevant non-major bleeding (RR 0.96, 95% CI: 0.65 to 1.42, = 0.0007). However, dabigatran is associated with an increased risk of gastrointestinal (GI) bleeding (RR 1.78, 95% CI: 1.02 to 3.13, = 0.05). Dabigatran has a favorable safety profile in terms of major bleeding, intracranial hemorrhage, and life-threatening events, among other safety outcomes. The present study suggested that dabigatran may be a suitable alternative to VKAs as an oral anticoagulant. However, more data are necessary to clarify the incidence of other adverse events and serious adverse reactions.
达比加群是一种单价低分子量直接凝血酶抑制剂，它是作为维生素K拮抗剂（VKA）的替代品而开发的。然而，迄今为止，达比加群的安全性仍存在争议。在本研究中，我们旨在通过对随机对照试验进行系统评价和荟萃分析，比较达比加群与对照组在出血风险、致命不良事件和全因死亡率方面的差异。我们系统检索了PubMed、Web of Science、Cochrane图书馆、Medline、Embase、万方数据库、临床试验、中国知网中文科技期刊数据库（维普）和中国生物医学数据库（CBM），以查找2014年1月至2020年7月期间发表的关于与达比加群相比的传统治疗的临床试验。对报告的结果，包括主要安全性终点进行了系统研究。本系统评价纳入了7项随机对照试验（n = 10743）。与对照组相比，达比加群与大出血风险增加无关（相对风险[RR] 0.86，95%置信区间[CI]：0.61至1.21，P = 0.06）、颅内出血（RR 0.89，95% CI：0.58至1.36，P = 0.41）、致命不良反应（RR 0.87，95% CI：0.65至1.17，P = 0.66）、全因死亡率（RR 0.88，95% CI：0.70至1.11，P = 0.45，I² = 0%），且临床相关非大出血风险显著降低（RR 0.96，95% CI：0.65至1.42，P = 0.0007）。然而，达比加群与胃肠道（GI）出血风险增加有关（RR 1.78，95% CI：1.02至3.13，P = 0.05）。在大出血、颅内出血和危及生命的事件等其他安全结果方面，达比加群具有良好的安全性。本研究表明，达比加群作为口服抗凝剂可能是VKA的合适替代品。然而，需要更多数据来阐明其他不良事件和严重不良反应的发生率。
