Uawithya Ekdanai, Saengphatrachai Weerawat, Srisurapanont Karan, Praditukrit Kulsatree, Kaveeta Chitapa
Division of Neurology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
J Stroke Cerebrovasc Dis. 2025 Aug;34(8):108371. doi: 10.1016/j.jstrokecerebrovasdis.2025.108371. Epub 2025 Jun 5.
Early initiation of direct oral anticoagulants (DOACs) after acute ischemic stroke (AIS) in patients with nonvalvular atrial fibrillation (NVAF) can prevent early recurrent AIS but may increase the risk of intracerebral hemorrhage (ICH). The appropriate DOAC initiation time remains uncertain. This systematic review and meta-analysis aimed to determine the optimal timing for DOAC initiation following NVAF-associated AIS.
We systematically searched PubMed, Embase, Scopus, and the Cochrane Library from inception to March 2025. Eligible studies were randomized controlled trials and prospective cohort studies examining the effects of DOAC initiation timing in patients with NVAF-associated AIS. The primary outcome was the pooled risk ratio for a composite measure of ischemic and hemorrhagic events. Secondary outcomes were the pooled risk ratios for symptomatic ICH, recurrent AIS, major extracranial bleeding, and mortality. Subgroup analyses examined patients initiating DOACs within 3 days of stroke onset and compared outcomes based on baseline stroke severity (NIHSS < 5 vs ≥ 5).
Eleven studies from ten cohorts (12,388 participants) met the inclusion criteria. No significant differences were found between early and delayed DOAC initiation for the composite outcomes or for any secondary endpoint. Subgroup analyses revealed a nonsignificant increase in ICH risk among patients with early treatment and higher stroke severity (NIHSS ≥ 5). No significant differences in early ischemic stroke rate were observed in both subgroups.
Early DOAC initiation appears to be safe following NVAF-associated AIS, including in patients with moderate stroke severity. However, the rate of early recurrent ischemic stroke remains comparable between early and delayed initiation groups.
非瓣膜性心房颤动（NVAF）患者急性缺血性卒中（AIS）后早期启动直接口服抗凝剂（DOACs）可预防早期复发性AIS，但可能增加脑出血（ICH）风险。合适的DOAC启动时间仍不确定。本系统评价和荟萃分析旨在确定NVAF相关AIS后DOAC启动的最佳时机。
我们系统检索了从创刊至2025年3月的PubMed、Embase、Scopus和Cochrane图书馆。符合条件的研究为随机对照试验和前瞻性队列研究，考察DOAC启动时间对NVAF相关AIS患者的影响。主要结局是缺血性和出血性事件综合指标的合并风险比。次要结局是症状性ICH、复发性AIS、主要颅外出血和死亡率的合并风险比。亚组分析考察了卒中发作3天内启动DOAC的患者，并根据基线卒中严重程度（美国国立卫生研究院卒中量表[NIHSS]<5 vs≥5）比较结局。
来自10个队列的11项研究（12388名参与者）符合纳入标准。早期和延迟启动DOAC在综合结局或任何次要终点方面均未发现显著差异。亚组分析显示，早期治疗且卒中严重程度较高（NIHSS≥5）的患者ICH风险有非显著增加。两个亚组的早期缺血性卒中发生率均未观察到显著差异。
NVAF相关AIS后早期启动DOAC似乎是安全的，包括中度卒中严重程度的患者。然而，早期和延迟启动组之间早期复发性缺血性卒中的发生率仍然相当。
