Early Versus Later Anticoagulation for Acute Ischemic Stroke in Patients With Atrial Fibrillation: A Systematic Review and Meta‐Analysis

Background: The optimal timing for initiating oral anticoagulation in patients with atrial fibrillation after acute ischemic stroke remains uncertain. This systematic review and meta-analysis aims to compare early versus later initiation of oral anticoagulants in this patient population. Methods: We systematically searched multiple databases, including MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov, up to January 2026. We included randomized controlled trials (RCTs) comparing early (≤ 4 days, post-stroke) versus later (> 5 days) direct oral anticoagulation (DOAC) initiation in patients with atrial fibrillation and acute ischemic stroke. Our main outcomes were a primary composite outcome of ischemic stroke, sICH, or unclassified stroke and the primary composite outcome, or all-cause mortality. Results: Four RCTs were included with a total of 6722 patients. Our meta-analysis revealed no significant difference between early and later DOAC initiation for the primary composite outcome (RR: 0.84, 95% CI: 0.64-1.10), primary composite outcome or mortality (RR: 0.99; 95% CI: 0.82-1.19), ischemic stroke (RR: 0.78, 95% CI: 0.54-1.12), symptomatic intracranial hemorrhage (RR: 1.00, 95% CI: 0.48-2.06), all-cause mortality (RR: 0.96, 95% CI: 0.80-1.14), or major bleeding (RR: 0.72, 95% CI: 0.33-1.60). Conclusion: Early initiation of anticoagulants appears to be comparable to later initiation in terms of stroke recurrence, bleeding risks, and mortality in patients with atrial fibrillation. These findings support a more individualized approach to anticoagulation timing, balancing ischemic and hemorrhagic risks based on patient characteristics. Further high-quality trials are needed to refine clinical guidelines and optimize anticoagulation strategies in this population. Trial Registration: CRD42024629570 [PROSPERO].