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

ABSTRACT 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