Abstract
BACKGROUND: The optimal timing of initiating direct oral anticoagulants (DOACs) after ischemic stroke in patients with atrial fibrillation (AF) remains uncertain. Early initiation may reduce recurrent stroke risk but raise concerns about hemorrhagic complications. This study aimed to evaluate the efficacy and safety of early versus later anticoagulation after ischemic stroke in AF. METHODS: We systematically searched PubMed, EMBASE, CENTRAL, and Scopus from inception to May 22, 2025, for randomized controlled trials (RCTs) comparing early (≤4 days) versus later (5-14 days) DOAC initiation post-stroke in AF. Primary outcomes were recurrent ischemic stroke, symptomatic intracerebral hemorrhage (sICH), and all-cause mortality. Data were pooled using MetaXL (version 5.3) with a random-effects model. Heterogeneity was assessed using the Chi-square test and I (2) statistic. RESULTS: Five RCTs (n = 6810) were included. Early anticoagulation showed a non-significant reduction in recurrent ischemic stroke (OR 0.80, 95% CI: 0.59-1.09; I (2) = 1%) and no significant difference in sICH (OR 0.92, 95% CI: 0.45-1.85; I (2) = 0%) or all-cause mortality (OR 0.94, 95% CI: 0.78-1.14; I (2) = 0%). Across all outcomes, heterogeneity was low and findings were consistent. CONCLUSION: Early initiation of DOACs after ischemic stroke in AF appears safe and may modestly reduce stroke recurrence without increasing hemorrhagic or mortality risk. These findings support individualized decision-making and suggest that early anticoagulation is a reasonable strategy in appropriately selected patients.