Abstract DP358: Age Subgroup Analysis of Anticoagulant Monotherapy Versus Combination Therapy in Patients With Ischemic Stroke and Nonvalvular Atrial Fibrillation - ATIS-NVAF trial -

Background: In the ATIS-NVAF randomized trial, anticoagulant monotherapy was compared with combination therapy (oral anticoagulant plus antiplatelet) in patients with ischemic stroke or transient ischemic attack (TIA), nonvalvular atrial fibrillation (NVAF), and atherosclerotic cardiovascular disease (ASCVD). Primary analysis showed no added ischemic benefit with combination therapy but increased bleeding. We aimed to determine whether treatment effects differed by age subgroup. Methods: Patients were enrolled 8–360 days after an index stroke or TIA and randomized 1:1 to anticoagulant monotherapy or combination therapy. Subgroups were younger (<75 years) and elderly (≥75 years). The primary endpoint was a composite of ischemic cardiovascular events and major bleeding within 2 years. Ischemic events included cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, and urgent revascularization. Secondary endpoints were all ischemic events, ischemic stroke, and myocardial infarction. Safety endpoints were ISTH major bleeding and intracranial hemorrhage (ICH). Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs), and the interaction between age and treatment was tested. Results: Among 316 patients (28% female; mean age 77.2 years), 199 were elderly (mean 81, 34.9% female) and 116 were younger (mean 69.4, 17.2% female). For the primary outcome, events occurred in 17.3% vs. 14.1% of younger and 17.3% vs. 16.8% of elderly (monotherapy vs. combination). HRs for combination vs. monotherapy were 0.84 (95% CI 0.34–2.10; p=0.705) in younger and 1.02 (0.52–1.99; p=0.947) in elderly, with no interaction (p=0.725). Similar null results were found for death, ischemic death, all ischemic events, ischemic stroke, and myocardial infarction (interaction p>0.4). For major bleeding, no interaction was seen (p=0.233), and risk of major plus clinically relevant non-major bleeding tended to increase in both groups (HR 2.25 younger, 2.02 elderly). For ICH, HRs were 0.12 (0.00–1.21; p=0.076) in younger and 2.12 (0.60–8.90; p=0.245) in elderly, with significant interaction (p=0.033). Conclusions: Combination therapy did not reduce ischemic outcomes compared with anticoagulant monotherapy in either age subgroup. However, a significant interaction for ICH suggested decreased risk in younger but increased risk in elderly. These findings highlight the need for individualized antithrombotic strategies, especially in older patients.