Yu Zhenglei, Zhu Wengen
Department of Cardiology, Sanming First Affiliated Hospital of Fujian Medical University, SanMing, China.
Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou of Guangdong, China.
Clin Appl Thromb Hemost. 2025 Jan-Dec;31:10760296251375864. doi: 10.1177/10760296251375864. Epub 2025 Sep 2.
The optimal timing for initiating direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) following acute ischemic stroke (AIS) remains a critical clinical question. This review evaluates findings from three pivotal randomized controlled trials-TIMING, ELAN, and OPTIMAS-comparing early versus delayed DOAC initiation in AF patients with AIS. Collectively, these trials provide strong evidence supporting the safety and efficacy of early initiation of DOACs in patients with AIS and AF. The TIMING trial demonstrated the non-inferiority of early DOAC initiation (≤4 days) compared to delayed initiation (5-10 days), with numerically lower rates of ischemic stroke and no cases of symptomatic ICH. The ELAN trial further corroborated these findings, showing no significant difference in the composite outcome of recurrent ischemic stroke, systemic embolism, or major hemorrhage between early initiation (≤48 h for minor/moderate strokes; days 6-7 for major strokes) and later initiation (days 3-4 to 12-14). OPTIMAS, the largest trial to date, confirmed the non-inferiority of early initiation (≤4 days) versus delayed initiation (7-14 days), without an increased risk of symptomatic ICH and with comparable rates of recurrent ischemic events.
对于急性缺血性卒中(AIS)后房颤(AF)患者,启动直接口服抗凝剂(DOACs)的最佳时机仍是一个关键的临床问题。本综述评估了三项关键随机对照试验(TIMING、ELAN和OPTIMAS)的结果,这些试验比较了AIS合并AF患者早期与延迟启动DOACs的情况。总体而言,这些试验提供了有力证据,支持在AIS和AF患者中早期启动DOACs的安全性和有效性。TIMING试验表明,与延迟启动(5 - 10天)相比,早期启动DOACs(≤4天)具有非劣效性,缺血性卒中发生率在数值上更低,且无有症状颅内出血(ICH)病例。ELAN试验进一步证实了这些结果,显示早期启动(轻度/中度卒中≤48小时;重度卒中第6 - 7天)与延迟启动(第3 - 4天至12 - 14天)在复发性缺血性卒中、系统性栓塞或大出血的复合结局方面无显著差异。OPTIMAS是迄今为止最大规模的试验,证实了早期启动(≤4天)与延迟启动(7 - 14天)相比具有非劣效性,无有症状ICH风险增加,且复发性缺血事件发生率相当。