New York—A common practice for cardiologists is to prescribe antithrombotic agents—specifically warfarin, a vitamin K antagonist—to prevent thromboembolic complications in patients after transcatheter aortic valve replacement (TAVR).

A new study suggests, however, that the anticoagulant edoxaban may be just as effective as warfarin for preventing heart attack or stroke in patients with atrial fibrillation (AF) who undergo TAVR.

The large-scale international study led by Mount Sinai, the ENVISAGE-TAVI AF trial, is the largest to investigate an edoxaban-based strategy in those patients. A report in The New England Journal of Medicine notes that edoxaban was found to be noninferior to warfarin.

The results, which could potentially be practice-changing, were recently announced in a late-breaking clinical trial at the European Society of Cardiology Congress 2021 and simultaneously published in NEJM.

“Atrial fibrillation after transcatheter aortic valve replacement is common, especially among older patients, but there has been little research on the optimal treatment strategies, and this has resulted in heterogeneous use of anticoagulants in clinical practice. 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,” explained lead investigator George Dangas, MD, PhD, professor of medicine (Cardiology) and director of cardiovascular innovation at Icahn School of Medicine at 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.”

Antithrombotic agents, most often warfarin, are prescribed to prevent thromboembolic complications after the minimally invasive heart procedure to replace the aortic valve. Finding the optimal antithrombotic regimen can be difficult, especially in patients with underlying conditions, such as AF.

Past research indicates that more than 30% of TAVR patients have AF and a large proportion of them are frail. That means the risks of bleeding and stroke must be balanced.

Researchers point out that the role of direct oral anticoagulants versus vitamin K antagonists for AF after successful TAVR has not been well studied.

To remedy that, the study team conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident AF as the indication for oral anticoagulation after successful TAVR.

Defined as the primary efficacy outcome for the industry-sponsored study was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding, with the last issue also being the primary safety outcome.

Ultimately, 1,426 patients were enrolled from 173 centers in 14 countries—713 in each group. Participants had a mean age of 82.1 years, and 47.5% of the patients were women. Almost all patients had AF before TAVR.

Results indicate that the rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = .01 for noninferiority).

Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03-1.91; P = .93 for noninferiority), and the authors explain that the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban.

On the other hand, rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66-1.11).

“In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events,” researchers conclude. “The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists.”

Researchers say they were surprised that patients who received a lower dose of edoxaban (30 mg instead of 60 mg) due to poor kidney function or low body weight appeared to have rates of adverse thromboembolic and bleeding events similar to those on warfarin.

“The next step would be to establish in large randomized trials the optimal anticoagulant dose according to different bleeding-ischemic risk profiles,” Dr. Dangas said. “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. We will be conducting a detailed analysis of various types of bleeding in the near future. ENVISAGE-TAVI AF suggests that treatment with edoxaban can be valuable in the management of this high-risk population of AF patients after TAVI.”

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