Rationale and design of a randomized trial of apixaban vs warfarin to evaluate atherosclerotic calcification and vulnerable plaque progression.

Vitamin K antagonists (VKAs) are known to increase vascular calcification, suggesting increased cardiovascular disease events. Apixaban is an oral direct factor Xa inhibitor superior to warfarin at preventing stroke or systemic embolism and may stabilize coronary atherosclerosis. The potential benefits of avoiding VKA therapy and the favorable effects of factor Xa inhibitors could contribute to cardiovascular disease event reduction. We hypothesized that apixaban inhibits vascular calcification and coronary atherosclerosis progression compared with warfarin in patients with atrial fibrillation (AF). This study is a single-center, prospective, randomized, open-label study. From May 2014 to December 2015, 66 patients with nonvalvular AF who experienced VKA therapy were enrolled. Patients were randomized into either warfarin or apixaban cohorts and followed for 52 weeks. The primary objective is to compare the rate of change in coronary artery calcification (CAC) from baseline to follow-up in apixaban vs warfarin cohorts. The key secondary objective is to compare the rate of incident plaques and quantitative changes in plaque types between patients randomized to either warfarin or apixaban cohorts using serial coronary computed tomography angiography. Expert readers will blindly assess CAC and coronary artery plaques. It is thought that this trial will result in significant differences in CAC and coronary artery plaque progression between the VKA and apixaban. The results are anticipated to provide a novel insight into treatment selection for AF patients. The study is registered at http://www.clinicaltrials.gov (NCT 02090075).

RCT Entities:   Population Interventions Outcomes