JAMA Neurol

What’s the optimal antithrombotic strategy for stroke patients with concurrent afib and atherosclerosis?

October 9, 2025

Study details: This randomized trial (NCT03062319) evaluated optimal antithrombotic regimens in patients with ischemic stroke and concurrent nonvalvular atrial fibrillation (NVAF) and atherosclerotic cardiovascular disease (ASCVD). The study compared oral anticoagulants (OACs), antiplatelet agents, and their combination for secondary prevention, focusing on recurrent stroke, major bleeding, and cardiovascular outcomes. Primary outcome was a composite of ischemic CV events and major bleeding within 2 years.

Results: The trial was terminated early for futility. Combination therapy didn't significantly reduce ischemic events (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.39-1.48; P = 0.41). The rate of the primary outcome was 17.8% in the combination therapy group and 19.6% in the monotherapy group (HR, 0.91; 95% CI, 0.53-1.55; P = .64). However, bleeding risk was significantly higher with combination therapy (19.5% vs. 8.6%; HR, 2.42; 95% CI, 1.23-4.76; P = 0.008).

Clinical impact: In patients with ischemic stroke, afib, and atherosclerosis, anticoagulant monotherapy remains the preferred strategy. Adding antiplatelet therapy increases bleeding risk without improving ischemic outcomes.

Source:

Okazaki S, et al; ATIS-NVAF Trial Investigators. (2025, October 6). JAMA Neurol. Optimal Antithrombotics for Ischemic Stroke and Concurrent Atrial Fibrillation and Atherosclerosis: A Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/41051787/