CLINICAL QUESTION: In patients with atherosclerotic disease and concurrent atrial fibrillation, does adding antiplatelet therapy to oral anticoagulation improve net clinical outcomes compared with anticoagulation alone?
BACKGROUND: Current guidelines recommend long-term oral anticoagulation (OAC) for patients with high-risk atrial fibrillation (AF), including those with ischemic stroke, and antiplatelet therapy for patients with symptomatic intracranial atherosclerosis or small vessel stroke. However, management becomes challenging when stroke, AF, and concomitant atherosclerotic disease coexist.
STUDY DESIGN: Randomized, open-label, clinical trial (ATIS-NVAF)
SETTING: Multicenter trial conducted at 41 hospitals in Japan
SYNOPSIS: The ATIS-NVAF trial randomized 321 patients with ischemic stroke within the prior year, AF, and coexisting atherosclerotic disease. They defined the latter as ischemic stroke from large artery atherosclerosis or small vessel occlusion; intracranial or carotid stenosis; or coronary or peripheral arterial disease. The primary outcome was the combination of ischemic events (stroke, myocardial infarction, vascular death, systemic embolism, or urgent revascularization) or major bleeding over two years. The primary outcome occurred in 19.6% of the monotherapy group and 17.8% of the combination group (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.53 to 1.55; P=0.64). Ischemic events were numerically lower with combination therapy, but major or clinically relevant nonmajor bleeding was significantly higher (19.5% versus 8.6%; HR, 2.42; 95% CI, 1.23 to 4.76, P=0.008). Limitations include the open-label design, modest sample size, and heterogeneity of antithrombotic regimens. The authors emphasize that the increased bleeding risk outweighs the uncertain ischemic benefit and caution against routine combination therapy outside specific indications, such as recent stenting.
BOTTOM LINE: In patients with stroke, atrial fibrillation, and atherosclerosis, routine addition of antiplatelet therapy to anticoagulation increases bleeding without improving net clinical outcomes.
CITATION: Okazaki S, et al. Optimal antithrombotics for ischemic stroke and concurrent atrial fibrillation and atherosclerosis: a randomized clinical trial. JAMA Neurol. 2025;82(12):1227-1234. doi: 10.1001/jamaneurol.2025.3662.
Dr. Alcuaz is a hospitalist at the clinical medicine department at Hospital Aleman and an instructor of internal medicine at the University of Salvador, both in Buenos Aires, Argentina.