Efficacy and Safety of Edoxaban in Anticoagulant Therapy Early After Surgical Bioprosthetic Valve Replacement: Rationale and Design of the Enbalv Trial

Abstract

Abstract Background and Purpose Anticoagulant therapy with vitamin K antagonists is recommended within 3 to 6 months after bioprosthetic valve replacement for preventing thromboembolic events, but data is limited about whether DOACs can be an alternative to warfarin in this situation. The purpose of the study is to evaluate the efficacy and safety of edoxaban compared with warfarin in patients within 3 months after bioprosthetic valve replacement.Methods The ENBALV trial is an investigator-initiated, phase 3, randomized, open-label, multicenter study. The subjects are patients undergoing bioprosthetic valve replacement at aortic and/or mitral position between 18 and 85 years of age. Patients are randomized 1:1 to receive either edoxaban or warfarin. Administration of edoxaban or warfarin is to be continued for 12 weeks after surgery. The primary outcome is the occurrence rate of stroke or systemic embolism at 12 weeks after surgery. The net clinical outcome is a composite of stroke, systemic embolism, or major bleeding, which is included in the secondary outcomes.Conclusion and Perspectives The first patient was enrolled in April 2022. We recruited 24 hospitals and we have enrolled 385 patients as of December 2023. ENBALV trial demonstrates the efficacy and safety of edoxaban compared with warfarin in patients early after bioprosthetic valve replacement including patients with sinus rhythm, which will bring a significant benefit to patients in clinical practice.Trial Registration Japan Registry of Clinical Trials (jRCT) 2051210209. Mar. 30, 2022 https://jrct.niph.go.jp/latest-detail/jRCT2051210209