Edoxaban ‘plausible alternative to warfarin’ to treat AF after TAVR
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In the ENVISAGE-TAVI AF trial, edoxaban was noninferior to vitamin K antagonists for adverse clinical events and was associated with increased major bleeding in patients with AF who underwent transcatheter aortic valve replacement.
The increase in major bleeding was primarily driven by gastrointestinal bleeding in the edoxaban (Savaysa, Daiichi Sankyo) group. Incidence of intracranial hemorrhage or fatal bleeding was rare in both groups.
“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. ... It is important to further understand what treatment is most effective to prevent devastating complications,” George Dangas, MD, PhD, professor of medicine and surgery at 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 noninferiority and edoxaban may be a plausible alternative to warfarin, albeit with attention to increased bleeding with this agent in this study population.”
The prospective, randomized, noninferiority ENVISAGE-TAVI AF trial enrolled 1,427 patients with prevalent or incident AF who underwent successful TAVR (mean age, 82 years; 48% women). Participants were randomly assigned to receive once-daily vitamin K antagonists or edoxaban 60 mg. Single or dual antiplatelet therapy was administered at the treating physicians’ discretion. Follow-up occurred at 3 months post-randomization and every 6 months thereafter.
The rate of the primary composite outcome of net adverse CV events, which included death from any cause, MI, ischemic stroke, systemic thromboembolism, valve thrombosis or major bleeding, was 17.3 per 100 person-years among patients assigned edoxaban and 16.5 per 100 person-years among those assigned vitamin K antagonists (HR = 1.05; 95% CI, 0.85-1.31; P for noninferiority = .014).
Major bleeding, the primary safety outcome 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 vitamin K antagonist group (HR = 1.4; 95% CI, 1.03-1.91; P for noninferiority = .93). The difference in major bleeding was primarily driven by increased gastrointestinal bleeding in the edoxaban group. Rates of intracranial hemorrhage or fatal bleeding were similarly low in both groups.
“In this type of population ... the major bleeding was not all that different between the two groups. ... The reason for the major bleeding was mostly major GI bleeding, in general, in this study,” Dangas said during a press conference.
The rate of death from any cause or stroke was 10 per 100 person-years among patients assigned edoxaban and 11.7 per 100 person-years among those assigned vitamin K antagonists (HR = 0.85; 95% CI, 0.66-1.11).
Among patients with a dose adjustment to 30 mg, rates of the primary efficacy and safety endpoints were similar to those in the vitamin K antagonist group.
The results were simultaneously published in The New England Journal of Medicine.
“The next step would be to establish in large randomized trials the optimal anticoagulant dose according to different bleeding-ischemic risk profiles,” Dangas said in the release. “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 on 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.”
Reference:
Perspective
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Deepak L. Bhatt, MD, MPH
This is a useful trial that provides further evidence generally supporting novel oral anticoagulants over warfarin, given their greater ease of use. Edoxaban was found to be noninferior to warfarin in patients with AF undergoing TAVR, a population that warranted further study. In places such as East Asia where edoxaban is used, it remains a reasonable alternative to warfarin. There was, however, more bleeding with edoxaban than warfarin in this trial, largely due to excess gastrointestinal bleeding. Practically speaking, I will likely stick with one of the other novel oral anticoagulants, with appropriate dosage adjustments per their labels.
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Dangas GD, et al. Hot Line: ENVISAGE-TAVI AF. Presented at: European Society of Cardiology Congress; Aug. 27-30, 2021 (virtual meeting).
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