ABSTRACT NUMBER: ESOC2026A1686 STROKE SEVERITY DICTATES OPTIMAL TIMING OF ORAL ANTICOAGULANT INITIATION IN ATRIAL FIBRILLATION-RELATED ACUTE ISCHEMIC STROKE: A NON-LINEAR MODELING ANALYSIS

Abstract Background and aims The optimal timing for initiating oral anticoagulants (OAC) after atrial fibrillation(AF)-related acute ischemic stroke remains controversial, particularly regarding the risk-benefit threshold within the "ultra-early" window (<48 hours). This study aimed to delineate the relationship between OAC initiation timing and outcomes. Methods We conducted a retrospective cohort study of 513 patients with atrial fibrillation-related acute ischemic stroke. Patients were stratified by National Institutes of Health Stroke Scale (NIHSS) scores into mild (<8) and moderate-severe (≥8) groups. We compared favorable outcomes and catastrophic outcomes (recurrent stroke or mortality) within 90 days between early (≤48 hours) and late (>48 hours) OAC initiation. Restricted cubic spline (RCS) regression and multivariate logistic regression were employed. Results In mild stroke (n=249), early OAC initiation showed no significant difference in favorable outcomes or catastrophic outcomes compared to late initiation, with RCS identifying the lowest mortality risk at 7 hours. Conversely, in the moderate-severe group (n=264), early initiation was associated with significantly higher catastrophic outcomes (36.7% vs. 12.4%, P <0.001) and was independently associated with a 4.52-fold increased risk of catastrophic outcomes (aOR 4.52, 95% CI 1.35–15.17). RCS analysis indicated that mortality risk in moderate-severe patients stabilized between 5 and 6 days (119–139 hours). Conclusions The safety of ultra-early OAC initiation is severity-dependent. While immediate initiation appears safe for mild stroke, initiating within 48 hours for moderate-severe stroke significantly increases mortality risk. A delay of 5–6 days is recommended for patients with moderate-severe deficits to minimize catastrophic outcomes. Conflict of interest Po-Lin Chen:nothing to disclose; Chi-Sheng Wang: nothing to disclose; Ting-Ya Chang: nothing to disclose.