Apixaban reduced recurrent stroke or systemic embolism compared to aspirin in cryptogenic stroke patients without high-risk hypertension features (HR 0.43; 95% CI 0.22-0.85).
RCT (n=945)
randomized
Yes
Does apixaban reduce recurrent ischemic stroke or systemic embolism compared to aspirin in patients with cryptogenic stroke and atrial cardiopathy, and is this effect modified by hypertension with high-risk features?
Apixaban reduces recurrent stroke risk compared to aspirin in cryptogenic stroke patients without high-risk hypertension features, suggesting that undiagnosed hypertensive arteriopathy may explain the failure of prior anticoagulation trials in this population.
Effect estimate: HR 0.43 (95% CI 0.22-0.85)
Importance Multiple trials have found no difference in secondary stroke prevention between anticoagulation and antiplatelet therapy after cryptogenic stroke. Due to limitations of current stroke mechanism classification, one possible explanation is the failure to exclude patients with hypertension-related cerebrovascular disease. Objective To determine whether hypertension with high-risk features is associated with treatment effect modification of anticoagulation vs antiplatelet therapy. Design, Setting, and Participants This exploratory analysis of the Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy (ARCADIA) randomized clinical trial was conducted between April and August 2025. The original trial was conducted from February 2018 to February 2023 at 185 sites in North America. From 1015 randomized patients with a recent cryptogenic stroke and atrial cardiopathy, 945 with available hypertension data were included in this analysis after exclusions for missing blood pressure and echocardiography data. Interventions Apixaban, 5 mg or 2.5 mg, twice daily vs aspirin, 81 mg, once daily. Main Outcomes and Measures The primary outcome was recurrent ischemic stroke or systemic embolism. Hypertension with high-risk features was defined as systolic blood pressure ≥160 mm Hg at enrollment, left ventricular hypertrophy on echocardiography, or both. Cox proportional hazards models evaluated treatment interaction with hypertension with high-risk features and estimated hazard ratios within hypertension with high-risk features subgroups. Results Among 945 patients (mean SD age, 68.0 10.8 years; 513 54.3% female), 351 (37.1%) met criteria for hypertension with high-risk features. Over a median (IQR) follow-up of 1.6 (0.7-3.0) years within the analytic cohort, 67 patients experienced a recurrent ischemic stroke or systemic embolism. A significant interaction between hypertension with high-risk features and antithrombotic treatment was observed. In 594 patients without hypertension with high-risk features, apixaban was associated with lower risk compared to aspirin (hazard ratio HR, 0.43; 95% CI, 0.22-0.85; annualized rate difference: −3.4%), whereas no significant association was observed in patients with hypertension with high-risk features (HR, 1.68; 95% CI, 0.78-3.62; annualized rate difference: 2.4%). Conclusions and Relevance The findings in this study indicate that hypertension with high-risk features may be associated with modifications in the effect of antithrombotic treatment in patients with cryptogenic stroke. An unappreciated inclusion of strokes due to hypertensive arteriopathy may account for the lack of benefit with anticoagulation in prior trials of embolic stroke of undetermined source. Trial Registration ClinicalTrials.gov Identifier: NCT03192215
Ridha et al. (Mon,) conducted a rct in Cryptogenic stroke and atrial cardiopathy (n=945). Apixaban vs. Aspirin, 81 mg, once daily was evaluated on Recurrent ischemic stroke or systemic embolism (HR 0.43, 95% CI 0.22-0.85). Apixaban reduced recurrent stroke or systemic embolism compared to aspirin in cryptogenic stroke patients without high-risk hypertension features (HR 0.43; 95% CI 0.22-0.85).