ABSTRACT NUMBER: ESOC2026A1807 NAVIGATING THE DIAGNOSTIC COMPLEXITY OF ISCHEMIC STROKE DESPITE ORAL ANTICOAGULANT THERAPY: DEVELOPING A SYSTEMATIC ALGORITHM-BASED APPROACH

Abstract Background and aims Anticoagulation decreases stroke risk in atrial fibrillation by 60–70%, yet breakthrough "anticoagulation failure"—the occurrence of an ischemic stroke despite therapy—remains a major clinical challenge requiring a detailed understanding of underlying mechanisms to guide secondary prevention. This study aims to investigate the specific mechanisms for ischemic stroke in patients receiving oral anticoagulant therapy. Methods This study utilized a three-step methodology: (1) a systematic review of PubMed articles to identify risk factors for stroke during anticoagulation; (2) development of a standardized questionnaire to assess stroke etiology; and (3) clinical evaluation of 26 patients presenting with breakthrough ischemic stroke. Results Among the 26 patients (median age 61 years; 41% women; 63% VKA, 37% DOAC), etiologies were classified as competing mechanisms (42%), insufficient anticoagulation (36%), and cardioembolism despite sufficient therapy (22%). First-line investigations focused on drug activity levels (INR for VKAs; anti-Xa or diluted thrombin time for DOACs), D-dimer, neuroimaging for silent infarcts, and vascular imaging to identify atherosclerotic plaques or aortic atheromas (>4 mm). Second-line assessments included hypercoagulable workups for Antiphospholipid Syndrome or genetic mutations, alongside advanced cardiac imaging such as 4D Flow MRI and Cardiac CT. Conclusions Stroke despite anticoagulation involves heterogeneous etiologies, where competing mechanisms and insufficient dosing are prevalent. Although DOACs were associated with better outcomes than VKAs, the findings emphasize the need for a systematic diagnostic algorithm. Differentiating between drug failure and competing vascular diseases through specific assays and advanced imaging is essential for tailoring individualized prevention strategies. Conflict of interest Mrinal Kumar Acharya: nothing to disclose; Anjan Debnath: nothing to disclose; Arvind K Jaiswal: nothing to disclose; K M Rao: nothing to disclose; Samir Rana: nothing to disclose