BACKGROUND: There are conflicting published data on the optimal timing of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with acute ischemic stroke. OBJECTIVE: To compare the efficacy and safety of early initiation of NOACs with later initiation of NOACs in those patients, we conducted a meta-analysis of phase 3 or phase 4 randomized controlled trials. METHODS: We systematically searched the Cochrane Library, PubMed, and Embase databases. A random effects model was selected to pool the effect measurement estimates (risk ratios [RRs] and 95% confidence intervals [CIs]). RESULTS: Three randomized controlled trials with 6442 enrolled patients with AF and acute ischemic stroke were included. Compared with later NOAC therapy, early NOAC therapy was associated with nonsignificant reductions in the risk of primary outcomes (RR, 0.82
95% CI, 0.65-1.05). Subgroup analysis found that in reducing risk of primary outcomes, early anticoagulation may benefit female patients more than male patients (0.54 [0.35-0.83] vs 0.97 [0.63-1.50]
P for interaction, .06). Numerically lower rates of recurrent ischemic stroke (RR, 0.80
95% CI, 0.56-1.15), death (RR, 0.96
95% CI, 0.81-1.15), and systemic embolism (RR, 0.43
95% CI, 0.16-1.11) were observed in early initiation of NOACs in comparison with later initiation of NOACs. There was no difference in major bleeding (RR, 0.98
95% CI, 0.55-1.74), symptomatic intracranial hemorrhage (RR, 0.93
95% CI, 0.43-1.96), or major extracranial bleeding (RR, 0.73
95% CI, 0.28-1.95) between groups. CONCLUSION: In AF patients with acute ischemic stroke, early initiation of NOACs is not inferior to later initiation of NOACs in reducing composite events, without increased hazard of bleeding, especially in female patients.