Comparison of early vs late anticoagulation for secondary stroke prevention in patients with atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials.

Patients with acute ischemic stroke (AIS) and atrial fibrillation (AF) have an increased risk of stroke recurrence. The optimal timing for initiating oral anticoagulation (OAC) for secondary stroke prevention remains uncertain. The recent OPTIMAS trial, the largest randomized controlled trial (RCT) to date on this topic, provides new insights. We therefore conducted a systematic review and meta-analysis of RCTs only, comparing early versus late initiation of OAC. We searched PubMed, Scopus, and Cochrane Central up to October 2024 for RCTs comparing early vs. late OAC initiation in AF patients with AIS. The Mantel-Haenszel method was used to calculate pooled odds ratios (ORs) for each outcome, with 95% confidence intervals (CI). We included three RCTs involving 6,442 patients; 50.17% received early OAC. There was no significant difference between groups in the composite outcome (OR 0.82; 95% CI: 0.63-1.06; p = 0.12). Stroke recurrence risk was similar (OR 0.80; 95% CI: 0.55-1.15; p = 0.23). Early OAC did not increase risk of mortality (OR 0.96; 95% CI: 0.79-1.16; p = 0.82), sICH (OR 0.93; 95% CI: 0.43-1.97; p = 0.84), or major extracranial bleeding (OR 0.73; 95% CI: 0.27-1.96; p = 0.54). Subgroup analysis showed early OAC in female patients reduced composite outcome risk (OR 0.51; 95% CI: 0.32-0.82; p = 0.005). Early OAC initiation after AIS in AF patients is safe but its benefit in reducing stroke recurrence is inconclusive and may be limited to specific subgroups. The addition of OPTIMAS, as the largest trial to date, strengthens the evidence base, confirming prior findings and providing additional confidence in the safety of early initiation. Until larger trials provide guidance, early OAC initiation should be considered case-by-case.