BackgroundThe impact of post-stroke antithrombotic regimen in atrial fibrillation (AF) is uncertain. ObjectiveTo describe antithrombotic therapy prescribing patterns following ischemic stroke, and its impact on outcomes. MethodsA total of 23,165 AF patients experiencing ischemic stroke were identified. Subsequent post-stroke events included recurrent ischemic stroke, intracranial hemorrhage (ICH), major bleeding, mortality, and composite outcomes. ResultsAmong those who were non-anticoagulated before a stroke, 33.5% remained non-anticoagulated and 39.2% were prescribed only antiplatelets (AP) post-stroke. Compared to NOACs post-stroke, there was a significant increase in ischemic stroke and mortality in non-anticoagulated (aHRs 2.09 and 3.92) and antiplatelet users (aHRs 1.32 and 1.28). Post-stroke warfarin was associated with a significantly incresaed risk of major bleeding compared to NOACs (aHR 1.23). Among 769 patients receiving NOACs before stroke and continuing NOAC post-stroke, those switching to a different NOAC were associated with significantly higher risk of ischemic stroke (aHR 2.07) and composite outcomes (aHRs 1.36-1.85) with no difference in ICH, major bleeding or mortality compared to those on the same NOAC post-stroke. Among patients receiving NOACs before stroke, the risks of clinical events were similar between patients on NOACs alone and those on NOAC plus AP post-stroke. ConclusionsNOAC alone post-stroke was associated with a better clinical outcome compared to non-anticoagulation, AP or warfarin. Among patients already taking NOACs before stroke, the addition of AP didn’t confer additional benefits compared to NOACs alone. A change of NOAC types post-stroke was associated with a two-fold higher risk of ischemic stroke and composite outcomes.