ABSTRACT NUMBER: ESOC2026A2404 CLINICAL AND FUNCTIONAL IMPACT OF THERAPEUTIC DIRECT ORAL ANTICOAGULANT LEVELS IN BREAKTHROUGH ISCHEMIC STROKE

Abstract Background and aims Breakthrough stroke occurs despite treatment with direct oral anticoagulants (DOACs), yet the clinical implications of DOAC plasma levels at stroke onset remain unclear. We investigated the association between DOAC plasma levels, acute ischemic stroke features, and 3-month functional outcome. Methods Between January 2024 and September 2025, we prospectively collected data from consecutive stroke code activations at our comprehensive stroke center. Patients with acute ischemic stroke and available DOAC plasma levels at admission were included. DOAC levels were categorized as therapeutic (≥50 ng/mL, tDOAC) or non-therapeutic (<50 ng/mL, ntDOAC). Associations with vessel occlusion, baseline stroke severity (NIHSS), and functional outcome at 3 months (mRS) were analyzed. Results Ninety-six patients had complete acute laboratory, clinical, and imaging data. DOAC plasma levels were not associated with LVO presence (p=0.63). Baseline stroke severity, LVO rates, and acute reperfusion treatments were similar between the both group. Patients with tDOAC levels had significantly lower rates of functional independence (mRS 0–2: 17.9% vs 42.4%; OD 0.30, 95% [0.11–0.78];p=0.012). A consistent trend toward fewer excellent outcomes (mRS 0–1) was observed (p=0.051). Patients with tDOAC levels had higher premorbid disability, and a trend toward greater vascular comorbidity burden, including hypertension, diabetes and heart failure, indicating greater baseline vulnerability. Conclusions In breakthrough AIS, tDOAC levels were not associated with reduced acute stroke severity or LVO occurrence but were linked to poorer functional outcome at 3 months. This dissociation may reflect increased frailty, comorbidity burden, and competing non-cardioembolic mechanisms in patients experiencing stroke despite adequate anticoagulation. Conflict of interest Federica Rizzo is supported by the Instituto de Salud Carlos III (CM24/00105), Marta Olive Gadea: is supported by the Instituto de Salud Carlos III (CM23/00280), Jorge Pagola is supported by Instituto de Salud Carlos III (FIS n.° PI24/00333), Carlos Molina, PI of two projects funded by the European Commission (TRUSTROKE_HE-HLTH-STAYHLTH2022 and UMBRELLA_HE_IHI2024). Giulio Fiore: nothing to disclose, Claudia Meza: nothing to disclose, Jesus Juega: nothing to disclose, Marta Rubiera: nothing to disclose. Marian Muchada: nothing to disclose.