ENVISAGE-TAVI AF is the first trial to compare edoxaban against standard of care in patients who have atrial fibrillation and have undergone successful TAVR.
Data from the ENIVSAGE-TAVI AF trial indicate edoxaban is noninferior to warfarin for adverse clinical events in patients with atrial fibrillation after transcatheter aortic valve implantation (TAVI).
The trial, which is the first to compare edoxaban against warfarin and its analogues in this patient population, was presented at the European Society of Cardiology (ESC) Congress 2021.
“TAVR patients are typically very elderly and possess numerous comorbidities; therefore, they are at high risk for all sorts of adverse events, both ischemic and bleeding. It is important to further understand what treatment is most effective to prevent devastating complications,” said principal investigator George Dangas, MD, PhD, professor of medicine and director of Cardiovascular Innovation at the Zena and Michael A. Wiener Cardiovascular Institute at the Icahn School of Medicine at Mount Sinai, in a statement from Mount Sinai. “Based on these results, the trial met its primary endpoint of non-inferiority and edoxaban may be a plausible alternative to warfarin, albeit with attention to increased bleeding with this agent in this study population.”
One of the most impactful advances within cardiology in recent memory, the popularity of TAVR procedures has ballooned in recent years. As cardiologists become more comfortable with the procedure, the focus in research has begun to shift from outcomes of the procedure to post-TAVR management. With this in mind, Edoxaban versus Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation–Atrial Fibrillation (ENVISAGE-TAVI AF) was designed to compare the safety and efficacy of edoxaban against vitamin K antagonists in patients with prevalent or incident atrial fibrillation following successful TAVR.
Sponsored by Daiichi Sankyo Inc, the prospective, randomized, open-label, adjudicator-masked trial was conducted from April 2017-January 2020 and randomized 1426 patients in a 1:1 ratio to edoxaban or a vitamin K antagonist, with 713 assigned to each arm. The multinational trial enrolled patients from 173 centers in 14 countries on 3 continents.
The primary efficacy outcome of the trial was a composite of adverse events consisting of all-cause mortality, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis or major bleeding. The primary safety outcome was incidence of major bleeding.
Patients included in the trial were 18 years of the or older and had either prevalent or incident atrial fibrillation lasting at least 30 seconds after successful TAVR for severe aortic stenosis. Investigators pointed out randomization occurred 12 hours to 7 days after TAVR and vitamin K antagonists examined in the study included warfarin, phenprocoumon, acenocoumarol, and fluindione.
The entire study cohort had a mean age of 82.1 years, 47.5% of patients were women, and 99% had atrial fibrillation before undergoing TAVR. During the follow-up period, which lasted a median of 554 days in the edoxaban group and 530 days in the vitamin K antagonist group, 215 (30.2%) patients in the edoxaban group and 289 (40.5%) in the vitamin K antagonist group discontinued treatment. Upon analysis, results indicate the rate of the composite primary efficacy outcome was 17.3 per 100 person-years among those in the edoxaban group and 16.5 per 100 person-years among those in the vitamin K antagonist group (HR, 1.05 [95% CI, 0.85-1.31]; P=.01for noninferiority).
When assessing rates of major bleeding, results indicated a rate of 9.7 per 100 person-years among those receiving edoxaban and 7.0 per 100 person-years among those receiving placebo therapy (HR, 1.40 [95% CI, 1.03-1.91]; P =.93 for noninferiority). Investigators noted the difference between groups seen in rates of major bleeding was driven primarily by an increase in gastrointestinal bleeding with edoxaban. Further analysis of adverse events suggested rates of death from any cause or stroke were 10.0 per 100 person-years among those receiving edoxaban and 11.7 per 100 person-years among those receiving a vitamin K antagonist (HR, 0.85 [95% CI, 0.66-1.11]).
“The next step would be to establish in large, randomized trials the optimal anticoagulant dose according to different bleeding-ischemic risk profiles,” Dangas added. “It seems that lowering the edoxaban dosage when indicated and avoiding patients with mandatory antiplatelet therapy because of their elevated bleeding risk is reasonable safety advice from the clinical point of view.”
This study was presented as “ENVISAGE-TAVI AF: edoxaban vs. vitamin K antagonists after TAVI in patients with atrial fibrillation“ at ESC Congress 2021 and simultaneously published as “Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR,” in the New England Journal of Medicine.