This systematic review and meta-analysis aimed to evaluate existing evidence on the optimal timing of anticoagulation initiation after ischemic stroke in patients with atrial fibrillation (AF). The goal was to determine whether early or delayed initiation leads to better clinical outcomes by balancing the risk of recurrent ischemic stroke against hemorrhagic complications, providing evidence-based guidance for clinical decision-making.

Following PRISMA guidelines (PROSPERO ID: CRD420250630978), eligible studies included randomized controlled trials and observational or interventional studies on adults (>18 years) with ischemic stroke and non-valvular AF comparing early versus delayed oral anticoagulation (OAC). Databases searched included Medline, PubMed, Scopus, OVID, Springer Nature, and Cochrane CENTRAL. Outcomes assessed included stroke recurrence, hemorrhagic transformation, major bleeding, mortality, functional outcomes, and thromboembolic events. Data extraction and bias assessment were performed independently, and meta-analyses using random-effects models were conducted with RevMan 5.4, reporting relative risk (RR) and 95% confidence intervals.

Seventeen studies (13 quantitative; >32,000 participants) showed no significant difference in all-cause mortality or major extracranial bleeding between early and delayed OAC initiation. Sensitivity analyses indicated that early anticoagulation reduced ischemic events and intracranial hemorrhage without increasing major bleeding risk.

Early OAC initiation after ischemic stroke in AF patients may lower ischemic and intracranial hemorrhage risks without increasing major bleeding. However, as most evidence is observational, high-quality randomized trials are needed to confirm these findings.