Edoxaban ‘plausible alternative to warfarin’ for treating AF after TAVR

In the ENVISAGE-TAVI AF trial, edoxaban was non-inferior to vitamin K antagonists for adverse clinical events and was associated with increased major bleeding in patients with AF who underwent aortic valve replacement with catheter.

The increase in major bleeding was mainly due to gastrointestinal bleeding in the edoxaban group (Savaysa, Daiichi Sankyo). The incidence of intracranial hemorrhage or fatal hemorrhage was rare in both groups.

“Atrial fibrillation after aortic valve catheter replacement is common, especially in older patients, but there has been little research on optimal treatment strategies, which has resulted in heterogeneous use of anticoagulants in clinical practice. … It is important to better understand which treatment is most effective in preventing devastating complications ”, George Dangas, MD, Ph.D., professor of medicine and surgery at the Icahn School of Medicine at Mount Sinai and director of cardiovascular innovation at the Zena and Michael A. Wiener Cardiovascular Institute at the Icahn School of Medicine at Mount Sinai, said in a press release. “Based on these results, the trial met its primary endpoint of non-inferiority and edoxaban may be a plausible alternative to warfarin, although attention is paid to increased bleeding with this agent in this study population. ”

The prospective, randomized ENVISAGE-TAVI AF non-inferiority trial included 1,427 patients with prevalent or incident AF who underwent successful TAVR (mean age, 82 years; 48% female). Participants were randomly assigned to receive vitamin K antagonists once daily or edoxaban 60 mg. Single or double antiplatelet therapy was given at the discretion of the attending physicians. Follow-up took place 3 months after randomization and every 6 months thereafter.

The composite primary endpoint rate of net adverse CV events, which included death from any cause, MI, ischemic stroke, systemic thromboembolism, valve thrombosis or major hemorrhage, was 17.3 per 100 person-years in patients receiving edoxaban and 16.5 per 100 people. -ans among those who received vitamin K antagonists (HR = 1.05; 95% CI: 0.85-1.31; P for non-inferiority = .014).

Major bleeding, the primary safety endpoint of the trial, occurred at a rate of 9.7 per 100 person-years in the edoxaban group and 7 per 100 person-years in the antagonist group. vitamin K (HR = 1.4; 95% CI: 1.03 -1.91; P for non-inferiority = .93). The difference in major bleeding was mainly due to an increase in gastrointestinal bleeding in the edoxaban group. The rates of intracranial hemorrhage or fatal hemorrhage were also low in both groups.

“In this type of population… the major bleeding was not that different between the two groups. … The reason for the major bleeding was primarily major gastrointestinal bleeding, in general, in this study, ”Dangas said at a press conference.

The death rate from all causes or strokes was 10 per 100 person-years in patients receiving edoxaban and 11.7 per 100 person-years in those receiving vitamin K antagonists (HR = 0.85 ; 95% CI: 0.66-1.11).

Among the patients with dose adjustment to 30 mg, the rates of the primary efficacy and safety endpoints were similar to those in the vitamin K antagonist group.

The results were published simultaneously in The New England Journal of Medicine.

“The next step would be to establish in large randomized trials the optimal dose of anticoagulant based on different profiles of ischemic bleeding risk,” Dangas said in the statement. “It appears that lowering the dose of edoxaban when indicated and avoiding patients on mandatory antiplatelet therapy because of their high risk of bleeding is clinically reasonable safety advice. We will soon conduct a detailed analysis of the different types of bleeding. ENVISAGE-TAVI AF suggests that treatment with edoxaban may be useful in the management of this high-risk population of patients with AF after TAVI.

Reference:

Perspective

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Deepak L. Bhatt, MD, MPH

This is a useful trial that provides additional evidence generally supporting new oral anticoagulants over warfarin. There was, however, more bleeding with edoxaban in this trial. In practice, I would probably stick with one of the other newer oral anticoagulants, with appropriate dosage adjustments according to their labels.

I don’t see much use of edoxaban around me. It is used in other parts of the world, so the data is particularly relevant for those regions. I would use one of the other newer oral anticoagulants in these types of patients.

Deepak L. Bhatt, MD, MPH

Cardiology today Editor of the intervention section

Brigham and Womens Hospital

Harvard Medical School

Disclosures: Bhatt says he served on the data security oversight committee for the ENVISAGE-TAVI AF trial and has financial ties to several companies that make antithrombotic therapies.

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