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

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.

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.

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.

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.