Purpose:To systematically review available evidence of indirect comparisons from RCTs and direct comparisons from observational studies regarding the comparative effectiveness and safety of DOACs in patients with AF. Methods: Electronic databases including EMBASE, MEDLINE, and PUBMED were searched up to June 5th, 2020. Primary endpoints included effectiveness (stroke or systemic embolism [SE]) and safety (major bleeding) outcomes. Bucher methods and random-effects models were conducted for indirect and direct comparisons among DOACs, respectively. Ranking probability analyses and the number needed to treat for net effect (NNTnet) were applied. Results: A total of 36 studies, involving 7 RCTs (n = 60,292 patients) and 29 observational studies (n = 1,164,821 patients), were included for analyses. Regarding the risk of stroke/SE, no significant differences were found from indirect comparisons of RCTs among the DOACs. For major bleeding, apixaban tended to be safer than rivaroxaban and dabigatran based on both direct and indirect comparisons (all p < 0.05; evidence quality: very low to moderate). Ranking probability analysis showed that apixaban had a high probability of being the best treatment in decreased risk of stroke/SE and major bleeding (80.30% and 91.30%, respectively). Likewise, apixaban was found to have the highest net clinical benefit (0.02, 95% CI: 0.014–0.029) and smallest NNTnet (48, 95% CI: 35–74). Conclusions: Apixaban appeared to have a favorable effectiveness-safety profile compared with the other DOACs in AF for stroke prevention, based on evidence from both direct and indirect comparisons. However, additional high-quality evidence is needed to support firm recommendations on clinical decision-making.

目的：系统地审查关于 DOACs 在 AF 患者中的比较有效性和安全性的 RCT 间接比较和观察性研究直接比较的现有证据。方法：检索了包括 EMBASE、MEDLINE 和 PUBMED 在内的电子数据库，截至 2020 年 6 月 5 日。主要终点包括有效性（卒中或全身性栓塞 [SE]）和安全性（大出血）结局。Bucher 方法和随机效应模型分别用于间接和直接比较 DOAC。应用了排名概率分析和净效应所需治疗数量 (NNTnet)。结果：共纳入 36 项研究，包括 7 项 RCT（n = 60,292 名患者）和 29 项观察性研究（n = 1,164,821 名患者）进行分析。关于卒中/SE 的风险，DOAC 之间 RCT 的间接比较没有发现显着差异。对于大出血，根据直接和间接比较，阿哌沙班往往比利伐沙班和达比加群更安全（所有p  < 0.05；证据质量：极低至中等）。排名概率分析表明，阿哌沙班很有可能成为降低卒中/SE 和大出血风险的最佳治疗方法（分别为 80.30% 和 91.30%）。同样，发现阿哌沙班具有最高的净临床益处 (0.02, 95% CI: 0.014–0.029) 和最小的 NNTnet (48, 95% CI: 35–74)。结论：根据来自直接和间接比较的证据，在 AF 中，与其他 DOAC 相比，阿哌沙班似乎在预防卒中方面具有良好的有效性 - 安全性。然而，需要额外的高质量证据来支持关于临床决策的坚定建议。