Apixaban to Prevent Covert Infarcts After Cryptogenic Stroke in Patients With Atrial Cardiopathy

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