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CHICAGO -- Edoxaban (Savaysa) appeared at least on par with warfarin for 12-week thromboembolic prophylaxis after bioprosthetic valve surgical implant in a Japanese trial with a population largely in sinus rhythm, but small numbers made the results inconclusive.

Edoxaban had a numerically lower rate of the primary outcome of stroke or systemic embolism at 0.5% compared with 1.5% on warfarin, but that represented just one event versus three over 12 weeks, reported Chisato Izumi, MD, PhD, of the National Cerebral and Cardiovascular Center in Osaka, Japan, at the American Heart Association (AHA) annual meeting.

At the same time, major bleeding occurred in 4.1% of the edoxaban-treated patients compared with 1.0% on warfarin (eight vs two events), none fatal or intracerebral with edoxaban compared with one fatal intracranial hemorrhage in the warfarin group.

"Since edoxaban does not require regular and frequent blood testing, it could simplify the care process during unstable conditions immediately after open-heart surgery and reduce the burden on patients and medical staff," Izumi said at an AHA press conference, suggesting that the direct oral anticoagulant (DOAC) could be an alternative for clinical use.

Current guidelines recommend anticoagulant therapy for 3-6 months following bioprosthetic valve replacement, including in patients with sinus rhythm, but only warfarin is recommended and approved for this group of patients.

Analysis of Society of Thoracic Surgeons Adult Cardiac Surgery data from 2020, showed a low but at the time of discharge after bioprosthetic valve surgery, despite this being off-label use for patients with sinus rhythm. Those researchers cautioned about the lack of safety data for this practice.

ENBALV was a proper comparison but still not definitive, said session study discussant P. Gabriel Steg, MD, of Hôpital Bichat in Paris.

"With four primary outcome events in total, we cannot conclude that edoxaban was comparable to warfarin in ENBALV," he cautioned. And with numerically higher major bleeding risk, "in my opinion, more work is needed to establish DOACs as a viable treatment option early after a bioprosthetic valve."

Even though DOACs are more practical than warfarin, managing bleeding early after surgery can be a problem, he noted.

AHA study discussant Manesh Patel, MD, of Duke University School of Medicine in Durham, North Carolina, pointed to the low event rate as evidence that many of these patients might not need to be anticoagulated at all.

"Many patients opt not to get a mechanical valve but get a bioprosthetic valve because they don't want to be on long-term warfarin therapy," he noted at the press conference.

The data suggest edoxaban can be considered, and it may give some reassurance to physicians who are already using it off-label in the non-atrial fibrillation (Afib) population after valve surgery, Patel agreed.

However, the data also suggest "this is a population that's at risk, but they may be at a low risk," he said. "It tells me our practice of not treating them is probably okay unless we figure out who's high risk."

More time probably needs to be spent figuring out just who is at high risk, although there aren't any good validated tools currently to do so, Patel said. Meanwhile, "in patients who don't have Afib, there may be some patients with bioprosthetic valves because of the [valve] size, the clot, the atrial size, patient risk factors, where I think they're at higher risk. So that patient might be a candidate."

The trial included 410 patients, ages 18-85, who received a surgical bioprosthetic aortic or mitral valve or both. Extremely high bleeding risk patients were excluded. Patients could have either sinus rhythm or Afib, which about 20% did. About 17% had been on an anticoagulant before trial enrollment.

Participants were randomized to 12 weeks on edoxaban at 30 or 60 mg once daily or warfarin once daily after which outcomes were measured. Treatment could be continued at the physicians' discretion, and median follow-up was 98 days.

The open-label design was a trial limitation. Steg also pointed out the low time in therapeutic range of only 19% in the warfarin group.

Hospital stays are becoming shorter, so it's difficult to achieve therapeutic range during that short stay, which is another reason to recommend DOACs early after surgery, Izumi argued.

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