Abstract A066: Oral Anticoagulant Monotherapy vs Oral Anticoagulant Plus Antiplatelet Therapy in Paroxysmal and Persistent Atrial Fibrillation: A Prespecified Subanalysis of the ATIS-NVAF Trial

Background: The ATIS-NVAF trial evaluated antithrombotic strategies in patients with nonvalvular atrial fibrillation (NVAF) and atherosclerotic cardiovascular disease (ASCVD) with prior ischemic stroke or transient ischemic attack (TIA). Whether adding an antiplatelet agent to oral anticoagulation (OAC) yields net clinical benefit may differ by atrial fibrillation (AF) type. Methods: In the ATIS-NVAF trial, patients with NVAF, ASCVD and prior stroke/TIA were randomized to either OAC monotherapy or OAC plus single antiplatelet therapy. The primary outcome was the 2-year composite of ischemic cardiovascular events and major bleeding. Secondary outcomes included individual ischemic events; safety outcomes included major and clinically relevant nonmajor (CRNM) bleeding. This prespecified subanalysis compared outcomes between OAC monotherapy and combination therapy, stratified by AF type (paroxysmal PAF vs persistent PeAF). Cumulative incidence rate was estimated by Kaplan–Meier method. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards models with Firth’s penalized. A treatment-by-AF-type interaction term was tested. Results: The PAF subgroup included 163 patients, and the PeAF subgroup included 152 patients. In the PAF subgroup, the 2-year cumulative incidence of the primary outcome was 16.3% with combination therapy and 14.3% in the OAC monotherapy (HR combination vs monotherapy 1.19, 95%CI 0.55-2.64, P=0.65). The incidence of major/CRNM bleeding was higher with combination therapy in PAF (20.9% vs 9.1%, HR 2.53, 95% CI 1.12-6.33, p=0.02). In the PeAF subgroup, neither the primary outcome (15.1% vs 20.3% with monotherapy; HR, 0.76; 95% CI, 0.35–1.61; p=0.48) nor bleeding differed between treatment groups. Ischemic event rates were similar between regimens regardless of AF type. No significant treatment by AF type interaction was detected. Conclusions: In patients with NVAF, ASCVD and prior ischemic stroke/TIA, adding an antiplatelet agent to OAC increased bleeding in PAF without reducing ischemic events and no advantage of combination therapy was observed in PeAF. OAC monotherapy may therefore be the safer option for patients with PAF in the absence of a clear ischemic benefit.