ABSTRACT NUMBER: ESOC2026A9 COMPETING ETIOLOGIES AND OUTCOMES AFTER BREAKTHROUGH ISCHEMIC STROKE IN PATIENTS WITH ATRIAL FIBRILLATION ON ORAL ANTICOAGULATION: RESULTS FROM THE ASPERA-R STUDY

Abstract Background and aims Patients with atrial fibrillation (AF) who suffer ischemic stroke despite oral anticoagulation (OAC) remain at elevated risk of recurrence and bleeding. We investigated whether competing stroke etiologies influence 90-day outcomes in this high-risk group. Methods ASPERA-R retrospectively enrolled adults (>18 years) with breakthrough ischemic stroke on OAC for AF, across 35 centers in 9 countries. Competing etiologies were defined as small-vessel disease, large-artery atherosclerosis (LAA), other determined or combined mechanisms. Patients without competing etiologies had cardioembolism as the sole identified cause. The primary outcome was 90-day recurrent ischemic stroke/TIA; secondary outcomes included mRS shift, myocardial infarction, vascular/all-cause death. Bleeding events were also evaluated. Inverse probability weighting (IPW) balanced baseline covariates; weighted Cox or regression models were applied. Results Among 1649 patients (mean age 78 years, 47.8% male), 24.3% had ≥1 competing etiology, most commonly LAA (59.9%). In the weighted cohort, 90-day recurrent ischemic stroke/TIA occurred more often in those with competing etiologies (6.0% vs 2.7%; aHR 2.17[95% CI 1.31–3.59];P = 0.003). Risk was greatest for LAA and other determined causes (RRs 2.20,[1.30–3.71] and 2.68,[1.27–5.66]). These patients also showed worse mRS (aOR 1.21,[1.01–1.45];P = 0.037) and higher all-cause mortality (aHR 1.29,[1.04–1.61];P = 0.021). Moderate-to-severe bleeding was more frequent with competing etiologies (aHR 1.94,[1.16–3.26];P = 0.021). Conclusions One in four patients had a competing etiology, most often LAA. This subgroup faced higher risks of recurrent ischemic events, functional dependence, mortality, and bleeding, highlighting the need for individualized secondary prevention. Conflict of interest Prof Casolla declares speaker’s fees from ACTICOR Biotech and SANOFI-AVENTIS France. Prof Sacco reports compensation from Novartis for other services; compensation from Novo Nordisk for consultant services; compensation from Boehringer Ingelheim for consultant services; compensation from Teva Pharmaceutical Industries for consultant services; compensation from Allergan for consultant services; employment by Università degli Studi dell’Aquila; compensation from Novartis for consultant services; compensation from Allergan for consultant services; compensation from PFIZER CANADA INC for consultant services; compensation from Abbott Canada for consultant services; compensation from H. Lundbeck A S for consultant services; compensation from AstraZeneca for consultant services; and. Figure 1 - belongs to Results