Open-Label Randomized Trial Comparing Oral Anticoagulation With and Without Single Antiplatelet Therapy in Patients With Atrial Fibrillation and Stable Coronary Artery Disease Beyond 1 Year After Coronary Stent Implantation

Abstract

Background: Despite recommendations in the guidelines and consensus documents, there has been no randomized controlled trial evaluating oral anticoagulation (OAC) alone without antiplatelet therapy (APT) in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) beyond 1 year after coronary stenting. Methods: This study was a prospective, multicenter, open-label, non-inferiority trial, comparing OAC alone to combined OAC and single APT among AF patients beyond 1 year after stenting in a 1:1 randomization fashion. The primary endpoint was a composite of all-cause death, myocardial infarction (MI), stroke, or systemic embolism. The major secondary endpoint was a composite of primary endpoint or major bleeding according to the International Society on Thrombosis and Haemostasis (ISTH) classification. Although the trial was designed to enroll 2,000 patients during 12 months, enrollment was prematurely terminated after enrolling 696 patients in 38 months. Results: Mean age was 75.0±7.6 years, and 85.2% of patients were men. OAC was warfarin in 75.2% and direct oral anticoagulants in 24.8% of patients. The mean CHADS₂ score was 2.5±1.2. During a median follow-up interval of 2.5 years, the primary endpoint occurred in 54 patients (15.7%) in the OAC alone group and in 47 patients (13.6%) in the combined OAC and APT group (HR, 1.16; 95% confidence interval [CI], 0.79-1.72; P=0.20 for non-inferiority; P=0.45 for superiority). The major secondary endpoint occurred in 67 patients (19.5%) in the OAC alone group and in 67 patients (19.4%) in the combined OAC and APT group (HR, 0.99; 95% CI, 0.71-1.39; P=0.016 for non-inferiority; P=0.96 for superiority). MI occurred in 8 (2.3%) and 4 (1.2%) patients, while stroke or systemic embolism occurred in 13 (3.8%) and 19 (5.5%) patients, respectively. Major bleeding occurred in 27 (7.8%) and 36 (10.4%) patients, respectively. Conclusions: This randomized trial did not establish non-inferiority of OAC alone to combined OAC and APT in patients with AF and stable CAD beyond 1 year after stenting. Because patient enrollment was prematurely terminated, the study was underpowered and inconclusive. Future larger studies are required to establish the optimal antithrombotic regimen in this population. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01962545.