Valvular Heart Disease: Edoxaban vs Warfarin in the ENGAGE AF-TIMI 48 Trial Interview with:
Raffaele De Caterina MD, PhD

Professor of Cardiology and Director of the University Cardiology Division
‘G d’Annunzio’ University in Chieti What is the background for this study? What are the main findings?

Response: The widely used term “valvular atrial fibrillation” encompasses a variety of conditions in which atrial fibrillation and valvular heart disease coexist. Since most trials of the non-vitamin K antagonist oral anticoagulants (NOACs) have variably excluded “valvular atrial fibrillation”, in more or less restrictive terms, there has been uncertainty whether NOACs can be used in such varied conditions. While atrial fibrillation in the presence of a mechanical valve or rheumatic mitral stenosis has to be a true contraindication (unfavorable data with one NOAC in the former setting; no data in the latter setting), patients with valvular diseases such as mitral insufficiency, aortic stenosis, aortic insufficiency, or with the presence of a bioprosthesis, have been variably included in the phase III trials of NOACs, but had not been extensively and conclusively studied before. What should readers take away from your report?

Response: Atrial fibrillation coexisting with valvular diseases such as mitral insufficiency, aortic stenosis, aortic insufficiency, or the presence of a bioprosthesis (in this last case: limited data) did not “interact” with the relative behavior of a NOAC – edoxaban – versus warfarin in the setting of the ENGAGE AF-TIMI 48 trial. This means that edoxaban 60 mg once daily – the dose currently approved – is at least as effective and safer than warfarin with or without those types of valvular heart disease. ENGAGE AF-TIMI 48 has been the largest study with a NOAC in atrial fibrillation, with a large group (2824 patients) of patients with those types of valvular heart disease studied, with the longest follow-up (median 2.8 years) available so far. What recommendations do you have for future research as a result of this study?

Response: Valvular diseases such as mitral insufficiency, aortic stenosis, aortic insufficiency can now be safely treated with a NOAC when atrial fibrillation is present. Atrial fibrillation in the presence of a bioprosthesis, especially during the first 3 months after the implant, has not been extensively studied, and although data appear reassuring, more data in such cases would be desirable and opportune, especially in the critical period of the first 3 months after an implant, where the vitamin K antagonists, such as warfarin, are currently indicated.. Is there anything else you would like to add?

Response: The term “valvular atrial fibrillation” should be simply abandoned, and has indeed disappeared in the latest edition of the European Society of Cardiology Guidelines. We had rather proposed the acronym “MARM-AF” (for mechanical valve and rheumatic mitral stenosis atrial fibrillation) to designate the entity where the use of NOACs is currently discouraged.

Disclosures: I have participated in all the 5 phase III trials of a NOAC in atrial fibrillation, and received grant funding and honoraria from all companies developing such drugs. Thank you for your contribution to the community.


Raffaele De Caterina, Giulia Renda, Anthony P. Carnicelli, FrancescoNordio, Marco Trevisan, Michele F. Mercuri, Christian T. Ruff, Elliott M.Antman, Eugene Braunwald, Robert P. Giugliano

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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