ENVISAGE-TAVI AF Compares Edoxaban Versus Vitamin K Antagonists After Valve Replacement in Patients With AF

August 28, 2021—The European Society of Cardiology (ESC) announced findings from the ENVISAGE-TAVI AF trial, which compared the safety and efficacy of the direct-acting oral anticoagulant (DOAC) edoxaban with vitamin K antagonists (VKAs; warfarin and its analogs) in patient with atrial fibrillation (AF) and an indication for oral anticoagulation after successful transcatheter aortic valve replacement (TAVR).

The study found that edoxaban is noninferior to warfarin and its analogs for adverse clinical events in patients with AF after TAVR, and the incidence of major bleeding was higher with edoxaban compared with VKAs. The findings were presented as late-breaking research in a Hot Line session at ESC Congress 2021, held virtually August 27-30. The study, “Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR” was published simultaneously by Nicolas M. Van Mieghem, MD, et al online in The New England Journal of Medicine.

As noted in the ESC announcement, the background of the study is that prevalence of pre-existing or new-onset AF after TAVR ranges from 20% to 40%. Oral anticoagulation is recommended to prevent stroke in patients with AF, but there is little information on the safety and efficacy of DOACs versus VKAs after TAVR.

Investigators in the ENVISAGE-TAVI AF trial enrolled 1,426 patients with AF from 173 medical centers in 14 countries on three continents. Patients in the study were randomly assigned to either edoxaban or the locally available VKA between 12 hours and 5 days after successful completion of TAVR.

The average age of patients was 82 years, and 47.5% were women. Comorbidities were common, including 83% to 87% with congestive heart failure, 39% to 42% with coronary artery disease, and approximately 17% with previous stroke or transient ischemic event. The average follow-up was 18 months.

The primary efficacy endpoint was a composite of adverse clinical events, including all-cause death, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, and major bleeding according to the International Society on Thrombosis and Hemostasis (ISTH) definition. The primary safety endpoint was the incidence of major bleeding according to the ISTH definition.

The investigator found that edoxaban was noninferior to VKAs for the primary composite endpoint of adverse clinical events. The rate of this endpoint was 17.5% per year in the edoxaban group and 16.5% per year in the VKA group (hazard ratio [HR], 1.05; 95% CI, 0.85-1.31; P = .01 for noninferiority).

Regarding safety, the edoxaban group had a higher risk of major bleeding compared to the VKA group, mainly caused by gastrointestinal bleeding. The rate of major bleeding was 9.7% per year in the edoxaban group and 7% per year in the VKA group (HR, 1.40; 95% CI, 1.03-1.91). In secondary analyses, patients in the edoxaban group who required a downward dose adjustment and those not prescribed oral antiplatelet therapy had a similar rate of major bleeding compared to the VKA group.

The study’s Principal Investigator is Professor George Dangas, MD, of the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai in New York, New York.

“Overall, this trial showed the noninferiority of edoxaban compared to warfarin (or similar analogs) with respect to the composite efficacy endpoint of adverse clinical events. On the other hand, we need to be attentive to the higher bleeding risks with edoxaban,” commented Prof. Dangas in the ESC press release. He continued, “Based on secondary analyses, it seems that lowering the edoxaban dosage when indicated and avoiding patients on mandatory antiplatelet therapy is reasonable safety advice from a clinical point of view. We will be conducting a detailed analysis on specific types of bleeding in the near future.”

Prof. Dangas concluded, “ENVISAGE-TAVI AF suggests that treatment with edoxaban can be valuable in the management of this high-risk population of patients with AF after TAVR.”