Doorbraakstroke onder DOAC's bij atriumfibrilleren vaak door niet-naleving of niet-cardioembolische oorzaken

BACKGROUND: Ischemic stroke may occur despite direct oral anticoagulant (DOAC) therapy in patients with atrial fibrillation (AF), yet the underlying mechanisms remain incompletely understood. Although a growing number of studies have addressed DOAC breakthrough stroke, data from Central and Eastern Europe (CEE) are scarce, despite substantial regional differences in vascular risk factor burden and patient comorbidity. PATIENTS AND METHODS: We retrospectively analyzed consecutive AF patients presenting with acute ischemic stroke while receiving DOAC therapy at a tertiary comprehensive stroke center in Szeged, Hungary (2022-2024). Patients were classified as pseudo-failure or true-failure based on predefined criteria reflecting anticoagulation adequacy (including non-compliance, off-label underdosing, drug interactions, and valvular AF). Clinical characteristics and etiologic distributions were compared, and logistic regression assessed the association between failure type and non-cardioembolic stroke mechanisms. RESULTS: Among 246 patients, 61.8% were classified as pseudo-failure, most commonly due to non-compliance and off-label underdosing, while 38.2% were true-failure. In the true-failure group, non cardioembolic mechanisms predominated, with large-artery atherosclerosis accounting for 41.5% of cases, whereas cardioembolism was less frequent (27.7%). True-failure status was independently associated with non-cardioembolic stroke mechanisms after multivariable adjustment (adjusted OR 7.15, 95% CI 3.85-13.29; p < 0.001). CONCLUSIONS: In this CEE cohort, DOAC breakthrough strokes were frequently attributable to pseudo-failure, whereas true-failure cases showed a high prevalence of competing non-cardioembolic mechanisms. This excess of alternative etiologies may reflect the higher vascular risk burden and greater multimorbidity characteristic of CEE populations, underscoring the need for systematic etiologic reassessment and mechanism-specific secondary prevention.