Key Points:
- In patients after surgical bioprosthetic valves, it remains unclear if edoxaban is safe and effective in preventing valve complicates early after surgery.
- In this randomized clinical trial, 389 patients who had surgical bioprosthetic valves implanted were randomized to receiving either standard dose endoxaban or warfar.
- Edoxaban was found to be as safe and effective treatment option to warfarin after surgical bioprosthetic valve implantation.
There is a high incidence of thromboembolic events after bioprosthetic surgical valves. Society guidelines recommend warfarin for 3-6 months following valve implantation. However, the off-label use of direct oral anticoagulants (DOACs) following bioprosthetic surgical valve implantation is rising although its efficacy and safety is unknown.
The Efficacy and Safety of Edoxaban in Anticoagulant Therapy Early After Surgical Bioprosthetic Valve Replacement (ENBALV) trial was an investigator-initiated, open-label, multicenter, randomized clinical trial performed at 24 institutions in Japan. The study enrolled 410 patients at 24 institutions in Japan who had bioprosthetic valve replacement at the aortic and/or mitral position between May 2022 and January 2024; 389 patients were included in the final analysis. Participants were randomized to receive either edoxaban (60 mg or 30 mg taken orally, once daily) or warfarin (administered orally, with dosing adjusted by monitoring the time taken for the patient’s blood to clot) for 12 weeks after surgery. The primary outcome was composite stroke or systemic embolism. The results of the trial were presented as a late breaking clinical trial at the American Heart Association on November 17, 2024.
Patients were ages 41-84 years old, with an average age of 73 years. The edoxaban group was 51% male and 49% female; the warfarin group was 63% male and 37% female. The study randomized participants after surgical bioprosthetic valve implantation in either the mitral or aortic position to either standard dose edoxaban (195 participants) or warfarin (194 participants).
A primary-outcome event occurred in 1 patient (0.5%) in the endoxaban arm and 3 patients (1.5%) in the warfarin arm (risk difference -1.03; 95% confidence interval [CI] -4.34 to 1.95) at 12 week follow-up. The incidence of major bleeding was higher in the endoxaban group compared to the warfarin group although not clinically significant (risk difference 3.07; 95% confidence interval [CI] –0.67 to 7.27). No fatal bleeding or intracranial hemorrhage was observed in the edoxaban group while one patient had fata intracranial bleeding in the warfarin group.
Limitations of the trial include open-label protocol, heterogenous initiation of anticoagulation at the discretion of the surgeon, short time in the therapeutic range for the warfarin arm (19.0% ± 21.6%), and no TAVR patients included.
In the late breaking presentation at the American Heart Association Scientific Sessions, Dr. Chisato Izumi concluded that “the ENBALV trial provides the first large-scale evidence demonstrating that edoxaban is a potential alternative anticoagulant therapy in patients early after bioprosthetic valve surgery.”