Early Versus Late Anticoagulation for Acute Ischemic Stroke in Atrial Fibrillation: A Systematic Review and Meta-Analysis of 17,380 Patients

Background/Objectives: The optimal timing for initiating oral anticoagulants (OACs) after acute ischemic stroke (AIS) in patients with atrial fibrillation (AF) remains uncertain due to potential risks of recurrent stroke and bleeding. This meta-analysis compares early versus late OAC initiation for recurrent ischemic stroke, major bleeding, intracranial hemorrhage (ICH), systemic embolism, and all-cause mortality. Methods: We conducted a meta-analysis of randomized controlled trials (RCTs), prospective, and retrospective observational studies. Data were pooled using random-effects models, and subgroup analyses were performed to assess outcomes by study design. Heterogeneity was quantified using I2 statistics. Results: A total of 17 studies were included. Early OAC initiation was associated with a significantly lower risk of recurrent ischemic stroke compared to late initiation (OR = 0.74, 95% CI 0.58, 0.95, p = 0.02), with moderate heterogeneity (I2 = 36%, p = 0.08). No significant difference was observed in ICH rates (OR = 0.74, 95% CI 0.41, 1.33, p = 0.32), major bleeding (OR = 1.48, 95% CI 0.51, 4.30, p = 0.47), or systemic embolism (OR = 0.65, 95% CI 0.33, 1.25, p = 0.20). All-cause mortality showed no difference between early and late initiation (OR = 1.00, 95% CI 0.72, 1.39, p = 0.99). Subgroup analyses were consistent with overall findings, and heterogeneity ranged from low to moderate across outcomes. Conclusions: Early initiation of OACs post-AIS in AF patients significantly reduces ischemic stroke recurrence without increasing risks of ICH, major bleeding, systemic embolism, or mortality. These findings support early anticoagulation strategies for selected patients.