Daiichi Sankyo Company, Limited has announced the results from the multinational, randomized, controlled, phase 3b ENVISAGE-TAVI AF study, comparing the efficacy and safety of edoxaban with vitamin-K-antagonists (VKAs) in patients with atrial fibrillation (AF) having undergone successful transcatheter aortic valve implantation (TAVI). Findings from the trial were presented at a Hot-Line session at ESC Congress 2021, organized by the European Society of Cardiology, and simultaneously published in The New England Journal of Medicine (NEJM). In ENVISAGE-TAVI AF, 1,426 elderly patients with multiple comorbidities were included and followed for up to three years. The study results suggest that edoxaban is an appropriate treatment option for AF patients with severe aortic stenosis following successful TAVI.1,2 To date, this is the only sufficiently large and statistically powered study that compares a non-vitamin K oral anticoagulant (NOAC) with VKAs in AF patients after TAVI. The study met its primary endpoint of edoxaban being noninferior to VKAs for the composite of net adverse clinical events (NACE), which included all-cause mortality, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, and International Society on Thrombosis and Haemostasis (ISTH)-defined major bleeding. NACE occurred in 170 edoxaban-treated patients (17.3% per year) and, similarly, in 157 VKA-treated patients (16.5% per year). Edoxaban also showed numerically lower rates of all-cause mortality and ischemic stroke (two of the six individual clinical events included in the composite of NACE): All-cause mortality occurred in 85 edoxaban-treated patients and 93 VKA-treated patients (7.8% versus 9.1% per year, respectively). Ischemic stroke occurred in 22 edoxaban-treated patients and 28 VKA-treated patients (2.1% versus 2.8% per year, respectively). The study did not meet its primary safety endpoint of ISTH-defined major bleeding, due to more gastrointestinal (GI) bleeds in the edoxaban arm.1,2 Other major bleeding events, including intracranial hemorrhage (ICH), as well as fatal and life-threatening bleeds, were similarly rare in both the edoxaban and VKA treatment arms: Major bleeding occurred in 98 edoxaban-treated patients and 68 VKA-treated patients (9.7% versus 7.0% per year, respectively).