Initiation of direct oral anticoagulation after reperfusion therapy in ischemic stroke in clinical practice: Results from Sits-International Stroke Registry

Introduction: Data is limited on the safety of early initiation of direct oral anticoagulation (DOAC) treatment after acute ischemic stroke (AIS) receiving reperfusion therapy in patients with atrial fibrillation (AF). We investigated the timing of DOAC initiation and its association with safety and outcomes.Materials and methods: We included AIS patients receiving reperfusion therapy with AF diagnosis (prevalent or new) registered in the Safe Implementation of Treatments in Stroke international registry during 2013-2024. Safety outcomes were hemorrhage and death. Secondary outcomes were recurrent AIS, any embolism and functional independence (modified Rankin Scale [mRS] 0-2) at 3 months. We performed descriptive statistics and multivariable analysis for DOAC initiation time as an ordinal variable (0-3, 4-7, and 8-100 days after stroke onset) and its association with outcomes. Explorative analyses were performed to investigate factors associated with DOAC initiation time, as a continuous or ordinal variable.Results: In total, 13,389 patients had data on DOAC initiation time, and 7861 patients had new event data by 3-month follow-up. We observed 0.1% intracranial hemorrhage, 0.4% major extracranial hemorrhage, 1.1% recurrent ischemic stroke, and 0.2% systemic embolism. At 3 months, 4.8% patients had died, and functional independence was seen in 60.9%. In multivariable analyses, DOAC initiation after stroke onset was not associated with any outcomes. Higher 24 h NIHSS and lower pre-stroke mRS score were associated with delayed DOAC initiation.Conclusion: DOAC initiation time was not associated with any outcomes in AIS patients who received reperfusion therapy. Severe stroke symptoms at 24 h were associated with delayed DOAC initiation. The low incidence of safety outcomes and missing data in this study should lead to cautious interpretations of these results.