ABSTRACT NUMBER: ESOC2026A1723 PREVALENCE AND POTENTIAL CONTRIBUTION OF ATHEROSCLEROSIS TO ISCHEMIC STROKES IN PATIENTS WITH ATRIAL FIBRILLATION ON ANTICOAGULATION

Abstract Background and aims The mechanisms underlying breakthrough strokes are incompletely understood. The association between carotid atherosclerosis and breakthrough strokes has not been sufficiently assessed. We aimed to determine the prevalence and potential contribution of carotid atherosclerosis to breakthrough strokes. Methods We analyzed data from the prospective, multicenter, observational RASUNOA-Prime study (ClinicalTrials.gov NCT02533960). Eligible patients had AF and an acute ischemic stroke. Patients were grouped by pre-stroke anticoagulation: direct oral anticoagulant (DOAC), vitamin K antagonist (VKA), or no oral anticoagulation. Stenosing and non-stenosing atherosclerosis including vulnerable plaques was assessed by core laboratory CTA readings. Associations of atherosclerotic manifestations with ipsilateral carotid-territory ischemia were examined using a generalized linear mixed model. Results Of 2,737 patients, CT angiography (CTA) was available for 1,464 (53.5%). Any carotid atherosclerosis was present in 81% of the 1,464 patients with available CTA. Overall, 17% had extracranial carotid stenosis ≥50% (NASCET) or carotid occlusion. Among 792 patients with unilateral carotid-territory ischemia and no stenosis, ipsilateral vulnerable carotid plaques were detected in 34% (28% non-OAC, 38% DOAC, 38% VKA), including bilateral plaques, whereas 5% had vulnerable plaques on the contralateral side only. In DOAC patients, the odds of ipsilateral vulnerable plaques were higher than in non-anticoagulated patients (OR = 4.4, 95% CI 1.6-11.8, P = 0.004). Conclusions Stenosing and non-stenosing carotid atherosclerosis with vulnerable plaques is an underestimated comorbidity in patients with breakthrough strokes which may contribute to the high risk of recurrence. Longitudinal studies including advanced vascular imaging are needed to better understand the impact of atherosclerosis to stroke recurrence after breakthrough strokes. Conflict of interest This was an investigator-initiated study funded by an unrestricted research grant to the Heidelberg University Hospital, Heidelberg, Germany. The RASUNOA-Prime study was supported by unrestricted grants to the Universitätsklinikum Heidelberg, Germany from Bayer Vital GmbH, Germany, Bristol-Myers Squibb/Pfizer Alliance, Boehringer Ingelheim Pharma GmbH & Co. KG, and Daiichi Sankyo Europe GmbH. The funding sources had no role in the design of the study, data collection, data analysis, or manuscript preparation, and no influence on the decision to submit the manuscript for publication. Alexander W Veltkamp: nothing to disclose. David Kinzler: nothing to disclose. Birte Hellwig: nothing to disclose. Adrian Heeger: nothing to disclose. Anika Huesing: nothing to disclose. Peter U. Heuschmann: research grants from, University Hospital Heidelberg (within RASUNOA-prime; supported by an unrestricted research grant to the University Hospital Heidelberg from Bayer, BMS, Boehringer-Ingelheim, Daiichi Sankyo); as well as from the German Ministry of Research and Education, Federal Joint Committee (G-BA), European Union, German Heart Foundation, German Research Foundation, Bavarian State, German Cancer Aid, Robert-Koch-Institute, outside the submitted work. Jan Purrucker: consultation fees and travel expenses from Abbott, Akcea, Bayer, Boehringer Ingelheim, Daiichi Sankyo, and BMS/Pfizer, and he reports grants from the Federal Joint Committee within the Innovation Fund. Roland Veltkamp: research support from European Union’s Horizon 2020 research and innovation program under grant agreement No 754517, and from Bayer, BMS-Pfizer, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, Biogen. Honoraria for consultancies and lectures for Astra Zeneca, Bayer, BMS-Pfizer, Javelin, Portola, and he is an investigator of the Imperial BRC.