Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Am J Cardiol. 2023 Oct 1;204:366-376. doi: 10.1016/j.amjcard.2023.07.108. Epub 2023 Aug 11.
Pivotal trials comparing direct oral anticoagulants (DOACs) against warfarin in patients with atrial fibrillation (AF) predominantly involved patients with high stroke risk. This study aimed to evaluate the efficacy and safety of DOAC versus warfarin in patients with low stroke risk. An online literature search was conducted to retrieve studies comparing clinical outcomes between patients treated with DOAC versus warfarin for AF, reporting outcomes for patients at low or minimal risk of stroke (CHADS-VASc scores ranging from 0 to 2 or CHADS scores ranging from 0 to 1). The primary outcome was the occurrence of stroke or systemic embolism. Secondary outcomes included major bleeding, intracranial hemorrhage, and all-cause mortality. Hazard ratios for all outcomes were pooled in random-effects meta-analyses. A network meta-analysis of individual DOACs versus warfarin was also conducted. In total, 11 studies (132,980 patients) were included. DOAC was associated with a significantly lower risk of stroke or systemic embolism (hazard ratio 0.85, 95% confidence interval 0.75 to 0.96, p = 0.008, I = 0%), major bleeding, intracranial hemorrhage, and mortality compared with warfarin. This benefit persisted even when study arms which had CHADS-VASc scores of 2 were excluded. When restricted to 3 studies investigating only patients with a single nongender-related stroke risk factor, significant benefit was seen only for the outcome of major bleeding. In the network meta-analysis, only dabigatran was superior to warfarin for all 4 outcomes. In conclusion, DOACs should be the standard of care in low-risk patients with AF who require anticoagulation. In particular, dabigatran appears to have the best balance of stroke prevention and reduction in major bleeding.
主要纳入高卒中风险房颤（AF）患者的直接口服抗凝剂（DOAC）与华法林的关键性试验。本研究旨在评估 DOAC 与华法林在低卒中风险 AF 患者中的疗效和安全性。通过在线文献检索，检索了比较 DOAC 与华法林治疗 AF 患者临床结局的研究，报告了卒中风险低或最低（CHADS-VASc 评分 0-2 分或 CHADS 评分 0-1 分）患者的结局。主要结局为卒中或全身性栓塞。次要结局包括大出血、颅内出血和全因死亡率。采用随机效应荟萃分析汇总所有结局的风险比。还对个体 DOAC 与华法林进行了网络荟萃分析。共纳入 11 项研究（132980 例患者）。与华法林相比，DOAC 显著降低了卒中或全身性栓塞（风险比 0.85，95%置信区间 0.75-0.96，p=0.008，I=0%）、大出血、颅内出血和死亡率的风险。即使排除 CHADS-VASc 评分为 2 的研究臂，这种获益仍然存在。当仅纳入 3 项仅研究单一非性别相关卒中危险因素的患者的研究时，仅主要出血结局显示出显著获益。在网络荟萃分析中，只有达比加群在所有 4 个结局方面优于华法林。总之，DOAC 应该成为需要抗凝治疗的低危 AF 患者的标准治疗方法。特别是，达比加群在预防卒中和减少大出血方面似乎具有最佳的平衡。
