Early versus delayed direct oral anticoagulants for secondary prevention after ischaemic stroke in patients with atrial fibrillation: A systematic review and meta-analysis

Abstract Background and Aims The optimal timing for direct oral anticoagulant (DOAC) initiation following acute ischaemic stroke in atrial fibrillation (AF) patients is clinically debated. While traditional practice favoured delayed initiation to prevent haemorrhagic transformation, recent trials suggest earlier therapy may reduce recurrent embolic events. This meta-analysis evaluates the efficacy and safety of early versus delayed DOAC initiation. Methods Systematic review of randomised controlled trials based on PRISMA 2020 Guideline was performed, including ELAN, TIMING, and OPTIMAS. Early initiation was defined as ≤4 days and delayed as 5–14 days post-stroke. The primary efficacy outcome was a composite of recurrent ischaemic stroke, systemic embolism, and all-cause mortality. The primary safety outcome was symptomatic intracranial haemorrhage (sICH). Statistical analysis was performed using RStudio with the meta package, employing a random-effects model to calculate pooled Risk Ratios (RR). Results Data from 6,210 participants showed early DOAC initiation significantly reduced the composite primary outcome (RR 0.81; 95% CI 0.66–0.98; p=0.03) compared to delayed initiation. Recurrent ischaemic stroke risk was numerically lower in the early group. Safety analysis revealed no significant increase in sICH (RR 1.02; 95% CI 0.44–2.37), regardless of stroke severity or prior reperfusion therapy. One-year follow-up confirmed a sustained safety profile. Conclusion Early DOAC initiation within 4 days of ischaemic stroke in AF patients is superior for preventing composite cardiovascular events and is safe across all stroke severities. These findings support early anticoagulation as the standard of care in acute stroke management.