Timing of anticoagulation therapy in patients with acute ischemic stroke and atrial fibrillation: a GRADE-based expert opinion recommendation

BACKGROUND: The optimal timing for initiating direct oral anticoagulants (DOACs) after acute ischemic stroke or transient ischemic attack (TIA) in patients with nonvalvular atrial fibrillation (NVAF) remains uncertain. OBJECTIVE: To determine whether early initiation of DOACs is superior to delayed initiation in preventing new vascular events. METHODS: This guideline was developed using the GRADE approach and includes a systematic review and meta-analysis of four randomized controlled trials (TIMING, ELAN, OPTIMAS, START) enrolling 6,664 patients. Outcomes were selected via Delphi consensus. Meta-analyses used random-effects models, with certainty of evidence rated per GRADE methodology. RESULTS: Early DOAC initiation was associated with a trend toward fewer recurrent ischemic events (RR 0.77, 95% CI 0.52-1.14) and thromboembolic events (RR 0.73, 95% CI 0.50-1.06), with no increase in symptomatic intracranial hemorrhage (RR 0.93, 95% CI 0.44-1.97) or major extracranial bleeding (RR 0.84, 95% CI 0.42-1.69). Certainty of evidence was low due to imprecision. An individual patient data meta-analysis from CATALYST collaboration further supported early treatment in patients with minor to moderate stroke. RECOMMENDATIONS: We recommend early DOAC initiation within 4 days in patients with minor to moderate stroke to prevent new vascular events. Early DOAC initiation over delayed treatment is indicated in patients with severe acute ischemic stroke to prevent new vascular events. CONCLUSION: Early DOAC initiation appears safe and potentially more effective than delayed treatment, supporting a shift toward earlier anticoagulation in selected patients with NVAF and recent ischemic stroke.