Optimal timing of anticoagulation after ischemic stroke in atrial fibrillation: a systematic review and network meta-analysis

BACKGROUND: Timing for anticoagulation (AC) initiation in atrial fibrillation (AF) after ischemic stroke (IS) remains uncertain. Previous large studies mostly represented high-income countries, with limited representation of severe stroke and low rates of primary outcomes. We aimed to compare AC initiation at different timeframes in a broader and more diverse population. METHODS: We searched Medline, Embase, Cochrane, and Clinical Trials for trials and observational studies comparing early versus late AC initiation in AF after IS. The study groups were 0-4, 5-14, and ≥ 15 days. Primary endpoints were recurrent IS only and intracranial hemorrhage (ICH). Secondary endpoints included systemic embolism, all-cause mortality, and major bleeding. Sensitivity analysis focused on studies using direct oral anticoagulants and timing categories consistent with our classification. RESULTS: Our meta-analysis included 20 studies with 25,884 patients. Mean NIHSS was 6.14, with at least 3204 severe strokes. IS was similar between groups, but the 0-4 days strategy ranked first (P-score = 0.92). Sensitivity analysis showed reduced recurrent IS in the 0-4 days group versus the ≥ 15 days group (RR, 0.28; 95% CI, 0.12-0.65; P < 0.01). ICH had no difference across all periods, 0-4 days versus 5-14 days (RR, 1.13; 95% CI, 0.58-2.18; P = 0.14); ≥ 15 days versus 5-14 days (RR, 0.91; 95% CI, 0.50 to 1.65; P = 0.75); and 0-4 days versus ≥ 15 days (RR, 0.87; 95% CI, 0.49-1.55; P = 0.63). No differences were observed in all secondary outcomes. CONCLUSION: Initiating AC 0-4 days after IS appears safe and may reduce the risk of recurrent stroke without increasing ICH, even in a more diverse population with higher-bleeding risk.