Author + information
- Nicolas Van Mieghem1,
- Marco Valgimigli2,
- Roxana Mehran3,
- Eric Boersma1,
- Usman Baber3,
- Christian Hengstenberg4,
- Minggao Shi5 and
- Roland Vranckx6
- 1Thoraxcenter, Erasmus Medical Center, Rotterdam, Netherlands
- 2Swiss Cardiovascular Center, Inselpsital, Bern, Switzerland
- 3Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Hospital, New York, New York, United States
- 4Deutsches Herzzentrum München, Munich, Germany
- 5Daiichi Sankyo Pharma Development, Basking Ridge, New Jersey, United States
- 6Hartcentrum Hasselt, Hasselt, Belgium
Patients with severe aortic stenosis and intermediate-to-high operative risk are often treated with transcatheter aortic valve implantation (TAVI). Up to 25–40% of TAVI patients have atrial fibrillation (AF) requiring chronic oral anticoagulation (OAC). In moderate-to-high risk AF patients, the direct factor Xa inhibitor edoxaban (EDOX) is noninferior to vitamin K antagonists (VKA) for prevention of stroke/systemic embolism with less bleeding and cardiovascular deaths.
ENVISAGE-TAVI AF will compare EDOX with VKA therapy in nonvalvular AF patients. Co-primary endpoints are net adverse clinical events (NACE; defined as the composite of all-cause death, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, and major bleeding) and major bleeding (International Society on Thrombosis and Haemostasis criteria).
ENVISAGE-TAVI AF is a multinational, multicenter, prospective, randomized, open-label, blinded-endpoint evaluation study in 1400 patients with AF after TAVI. Patients will be randomized 1:1 to EDOX 60 mg (dose reduced to 30 mg if a patient meets the dose reduction criteria based on label) or VKA (dosed to attain an international normalized ratio of 2.0–3.0 [1.6–2.6 in Japanese patients aged ≥70 years]) 12 hours to 5 days after successful TAVI. Antiplatelet therapy may be administered per physician discretion. Randomization will be stratified by OAC dose reduction. Treatment duration will be up to 36 months (≥6 months for last patients enrolled) or until a patient reaches a primary endpoint. The study is powered (80%) to detect noninferiority for NACE and major bleeding (noninferiority margin: 1.38) followed by superiority testing for major bleeding and NACE at a significance level of α = 0.05. Secondary endpoints will include analyses of NACE components.
ENVISAGE-TAVI AF compares the clinical safety and efficacy of EDOX vs VKA in nonvalvular AF patients with the indication for OAC after successful TAVI. At present, this is the only TAVI study that compares exclusively nonvalvular AF patients receiving a non-VKA OAC vs a VKA-based therapy. (ClinicalTrials.gov NCT02943785 )
ENDOVASCULAR: Stroke and Stroke Prevention