Efficacy and Safety of Edoxaban in Anticoagulant Therapy Early After Surgical Bioprosthetic Valve Replacement: A Randomized Clinical Trial

BACKGROUND: Anticoagulant therapy with vitamin K antagonists is recommended in the current guidelines for 3 to 6 months following bioprosthetic valve replacement. However, in the era of direct oral anticoagulants, there is a paucity of evidence regarding the efficacy and safety of direct oral anticoagulants in this patient group. METHODS: The ENBALV trial (Edoxaban in Anticoagulant Therapy After Surgical Bioprosthetic Valve Replacement) was an investigator-initiated, phase 3, randomized, open-label, multicenter study that aimed to evaluate the efficacy and safety of edoxaban compared with warfarin within 3 months following bioprosthetic valve replacement at the aortic or mitral position or both. The primary outcome was stroke or systemic embolism. The secondary outcomes included major bleeding, intracardiac thrombus, and a composite of stroke, systemic embolism, or major bleeding. Given the limited study period and the low event rate of the primary outcome, this study assessed the difference in the point estimates of the event rate. RESULTS: Of the 410 enrolled patients, 389 were included in the final analysis (73±6 years, 56.8% male, 79.4% sinus rhythm; edoxaban group: n=195, warfarin group: n=194). The primary outcome occurred in 0.5% (n=1) in the edoxaban group, whereas in 1.5% (n=3) in the warfarin group (risk difference, -1.03% [95% CI, -4.34 to 1.95%]). Major bleeding occurred in 4.1% (n=8) in the edoxaban group and in 1.0% (n=2) in the warfarin group (risk difference, 3.07% [95% CI, -0.67 to 7.27%]). No fatal bleeding or intracranial hemorrhage was observed in patients treated with edoxaban, whereas 1 fatal intracranial hemorrhage occurred in the warfarin group. Intracardiac thrombus did not occur in any of the patients in the edoxaban group, but did occur in 1.0% (n=2) in the warfarin group. CONCLUSIONS: Edoxaban is a potential alternative anticoagulant therapy early after bioprosthetic valve replacement. REGISTRATION: URL: https://jrct.niph.go.jp/latest-detail/jRCT2051210209; Unique identifier: jRCT2051210209.