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Edoxaban noninferior to warfarin for adverse events after heart valve replacement

ENVISAGE-TAVI AF study presented in a Hot Line Session today at ESC Congress 2021

Device Therapy
Atrial Fibrillation

Sophia Antipolis, France – 28 Aug 2021:  Edoxaban is noninferior to warfarin and its analogues for adverse clinical events in patients with atrial fibrillation after transcatheter aortic valve implantation (TAVI). That’s the finding of late breaking research presented in a Hot Line session today at ESC Congress 20211 and published in the New England Journal of Medicine.2 The incidence of major bleeding was higher with edoxaban compared with vitamin K antagonists (VKAs).

The prevalence of pre-existing or new-onset atrial fibrillation after TAVI ranges from 20% to 40%.3-8 Oral anticoagulation is recommended to prevent stroke in patients with atrial fibrillation but there is little information on the safety and efficacy of direct-acting oral anticoagulants (DOACs) versus VKAs after TAVI.

ENVISAGE-TAVI AF compared the safety and efficacy of the DOAC edoxaban with VKAs (warfarin and its analogues) in atrial fibrillation patients with an indication for oral anticoagulation after successful TAVI. The trial enrolled 1,426 patients with atrial fibrillation from 173 medical centres in 14 countries on three continents. Participants were randomly assigned to either edoxaban or the locally available VKA between 12 hours and five days after successful completion of TAVI.

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

The average age of participants was 82 years and 47.5% were women. Comorbidities were common: for example, 83–87% had congestive heart failure, 39–42% had coronary artery disease, and approximately 17% had a previous stroke or transient ischaemic event.

The average follow-up was 18 months. 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% confidence interval [CI] 0.85–1.31; p=0.01 for noninferiority).

Regarding safety, the edoxaban group had a higher risk of major bleeding compared to the VKA group, mainly due to gastrointestinal bleeding. The rate of major bleeding was 9.7% per year in the edoxaban group and 7.0% 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.

Principal investigator Professor George Dangas of the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, US said: “Overall, this trial showed the noninferiority of edoxaban compared to warfarin (or similar analogues) 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. 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.”

He concluded: “ENVISAGE-TAVI AF suggests that treatment with edoxaban can be valuable in the management of this high-risk population of patients with atrial fibrillation after TAVI.”



Notes to editor

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This press release accompanies both a presentation and an ESC press conference at ESC Congress 2021. It does not necessarily reflect the opinion of the European Society of Cardiology.

Funding: The ENVISAGE-TAVI AF trial was funded by Daiichi-Sankyo

Disclosures: GD’s institution has received research grants from Daiichi-Sankyo and GD has lectured about this clinical condition.

References and notes

1ENVISAGE-TAVI AF: edoxaban vs. vitamin K antagonists after TAVI in patients with atrial fibrillation.

2 Dangas G et al. Edoxaban vs Vitamin K Antagonists for Atrial Fibrillation After Transcatheter Aortic Valve Replacement (ENVISAGE-TAVI AF). N Engl J Med. 10.1056/NEJMoa2111016

3Mack MJ, Leon MB, Thourani VH, et al. Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med. 2019;380:1695–1705.

4Holmes DR, Nishimura RA, Grover FL, et al. Annual outcomes with transcatheter valve therapy: from the STS/ACC TVT Registry. J Am Coll Cardiol. 2015;66:2813–2823.

5Tarantini G, Lefèvre T, Terkelsen CJ, et al. One-year outcomes of a European transcatheter aortic valve implantation cohort according to surgical risk: subanalysis of the SOURCE 3 Registry. Circ Cardiovasc Interv. 2019;12:e006724.

6Reardon MJ, Van Mieghem NM, Popma JJ, et al. Surgical or transcatheter aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2017;376:1321–1331.

7Popma JJ, Deeb GM, Yakubov SJ, et al. Transcatheter aortic-valve replacement with a self-expanding valve in low-risk patients. N Engl J Med. 2019;380:1706–1715.

8Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2016;374:1609–1620.

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