Early versus later non-vitamin K antagonist oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation: A meta-analysis and systematic review of randomized trials.

Background: There are conflicting published data on the optimal timing of 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 NOACs initiation with later NOACs initiation in those patients, we conducted a meta-analysis of phase III or IV randomized controlled trials (RCTs).

Methods: We systematically searched the Cochrane Library, PubMed, and Embase databases. A random-effect model was selected to pool the effect measurement estimates (Risk Ratios [RRs] and 95% confidence intervals [CIs]).

Results: Three RCTs with 6,442 enrolled patients with AF and acute ischemic stroke were included. Compared with later NOAC therapy, early NOACs therapy was associated with non-significant reductions in the risk of primary outcomes (RR 0.82, 95% CI 0.65-0.1.02). Subgroup analysis showed that female patients may benefited more from early anticoagulation in reducing risk of primary outcomes than male patients (0.54, 0.35-0.83 vs 0.97, 0.63-1.50; P for interaction 0.06). 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 NOACs initiation in comparison with later NOACs initiation. There was no difference in major bleeding (RR 0.98, 95% CI 0.55-1.74), symptomatic intracranial haemorrhage (RR 0.93, 95% CI 0.43-1.96), or major extracranial bleeding (RR 0.73, 95% CI 0.28-1.95) between both 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, which significantly reduce composite events.