Apixaban to Prevent Covert Infarcts After Cryptogenic Stroke in Patients With Atrial Cardiopathy: A Secondary Analysis of the ARCADIA Randomized Clinical Trial

Importance: In the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) randomized clinical trial, anticoagulation did not prevent recurrent stroke among patients with a recent cryptogenic stroke and atrial cardiopathy. It is unknown whether anticoagulation prevents covert infarcts in this population. Objective: To test the use of apixaban vs aspirin for prevention of nonlacunar covert infarcts after cryptogenic stroke in patients with atrial cardiopathy. Design, Setting, and Participants: ARCADIA-MRI, an ancillary study to the ARCADIA trial with a median follow-up period of 27 months, enrolled participants from 75 sites in the US from November 14, 2019, until December 2, 2022. Participants in ARCADIA were invited to coenroll in ARCADIA-MRI if they had not permanently discontinued the study drug and had no contraindications on magnetic resonance imaging (MRI). A total of 310 (31%) of the 1015 ARCADIA participants enrolled in ARCADIA-MRI and of those 174 (56%) with adequate quality baseline and follow-up MRI were included in the present analyses. Interventions: MRI performed at the time of the index stroke served as the baseline image unless it was unavailable or of insufficient quality, in which case a new research MRI was obtained. A follow-up research MRI was performed upon each participant's completion of participation in the ARCADIA parent study. Main Outcomes and Measures: The primary outcome was incident nonlacunar covert infarct on the follow-up MRI assessed by 2 independent raters who were masked to treatment assignment. Results: Baseline characteristics were balanced between the apixaban (n = 79) and aspirin (n = 95) arms. The mean (SD) age was 66 (10.6) years, and the median (IQR) modified Rankin Scale (mRS) score 1 (0-2). Ninety-one participants (52.3%) were male. During the median (IQR) follow-up of 811 (487-1288) days, the risk of incident nonlacunar covert infarcts was lower in the apixaban group (5.1%) than the aspirin group (17.9%) (weighted relative risk, 0.29; 95% CI, 0.10-0.83). Conclusions and Relevance: Apixaban compared to aspirin was associated with fewer incident nonlacunar covert infarcts among a subset of patients with a recent cryptogenic ischemic stroke and atrial cardiopathy who were enrolled in ARCADIA. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.