Antithrombotic Therapy for Secondary Stroke Prevention in Patients With Symptomatic Large‐Artery Atherosclerosis and Atrial Fibrillation: A Multicenter Experience

BACKGROUND: Optimal antithrombotic therapy for ischemic stroke due to symptomatic large-artery atherosclerosis in patients with atrial fibrillation remains uncertain. We describe real-world prescribing patterns and outcomes across antithrombotic regimens. METHODS: We retrospectively analyzed consecutive patients with atrial fibrillation and ischemic stroke related to symptomatic large-artery atherosclerosis (intracranial or extracranial or both) at 4 US comprehensive stroke centers. Patients were grouped by discharge regimen: single anticoagulant, single antiplatelet (sAP), single anticoagulant+sAP, dual antiplatelet therapy, or triple therapy (single anticoagulant+dual antiplatelet therapy). Outcomes were recurrent ischemic stroke, symptomatic hemorrhage, and death at 90 days and 1 year. RESULTS: Among 191 patients (median age 75 years [interquartile range [IQR], 68-83]; 40% women; 36% prior stroke/transient ischemic attack), single anticoagulant+sAP was the most common discharge regimen (33%), followed by single anticoagulant (25%), whereas triple therapy was uncommon (4%). More than half of patients switched regimens within 1 year, mostly as the planned duration ended (71%) or following an outcome event (12%). During follow-up (median 68 days [IQR, 28-120]), 21 patients (11%) had recurrent ischemic stroke, and 26 (14%) had symptomatic hemorrhage, over half of each within 90 days; 25% of deaths occurred within 90 days. Ninety-day stroke/death rate was 24%, with single anticoagulant versus 8% with single anticoagulant+sAP; symptomatic hemorrhage rate was 0% and 12%, respectively. At 1 year, stroke/death was 27.3% with sAP, 11.1% with single anticoagulant+sAP, 4.5% with single anticoagulant, and 0% with dual antiplatelet therapy. Symptomatic hemorrhage was similar across groups. CONCLUSIONS: In patients with atrial fibrillation and symptomatic large-artery atherosclerosis, recurrent ischemic events and mortality were common, and antithrombotic management varied substantially. The combination of single anticoagulant+sAP was associated with lower observed short-term stroke/death than single anticoagulant; however, bleeding remains a concern with prolonged therapy. Prospective studies are needed to define optimal regimen and duration for this high-risk population.