Prevalence and Association of Atherosclerosis to Ischemic Stroke in Patients With Atrial Fibrillation on Anticoagulation

BACKGROUND: Approximately, 20% of ischemic strokes in patients with atrial fibrillation occur despite anticoagulation. These breakthrough strokes are associated with a high risk of recurrence, but underlying mechanisms remain incompletely understood. In particular, the association between carotid atherosclerosis and breakthrough strokes has not been sufficiently assessed. METHODS: We analyzed data from the prospective, multicenter, RASUNOA-Prime cohort study (Registry of Acute Stroke Under Novel Oral Anticoagulants–Prime), conducted at 46 German stroke centers between 2015 and 2020. Eligible patients had atrial fibrillation and an ischemic stroke within 24 hours before admission. Of 2737 patients, computed tomography angiography was available for 1464 (53.5%). Patients were grouped according to prestroke anticoagulation with direct oral anticoagulants, vitamin K antagonists, or no oral anticoagulation. Carotid atherosclerosis, including stenosis or occlusion and nonstenosing vulnerable plaques, was assessed by core laboratory computed tomography angiography readings. Carotid arteries served as observational units, with presence of atherosclerosis as binary outcome and laterality of carotid-territory ischemia as explanatory variable in generalized linear mixed models. Laterality of atherosclerosis was assessed as ipsilateral if present on the side of carotid-territory ischemia. RESULTS: Any carotid atherosclerosis was identified in 81% of 1464 patients with available computed tomography angiography. Extracranial carotid stenosis ≥50% or occlusion was present in 17%. Among 792 patients with unilateral carotid-territory ischemia and no stenosis, ipsilateral vulnerable carotid plaques were detected in 34% (no oral anticoagulation 28%, direct oral anticoagulants 38%, vitamin K antagonists 38%), including patients with bilateral plaques, whereas 5% had contralateral vulnerable plaques only. In direct oral anticoagulant–treated patients, odds of ipsilateral vulnerable plaque were significantly higher than in nonanticoagulated patients (odds ratio, 4.4 [95% CI, 1.6–11.8]; P =0.004). CONCLUSIONS: Stenosing and nonstenosing carotid atherosclerosis represents a frequent comorbidity in patients with breakthrough strokes, which may contribute to their high risk of recurrence. Longitudinal studies including advanced vascular imaging are needed to clarify the impact of atherosclerosis on stroke recurrence after breakthrough strokes in patients with atrial fibrillation. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02533960.