Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes

Paulus Kirchhof1, Tobias Toennis1, Andreas Goette1

  • 1From the Atrial Fibrillation Network, Münster (P.K., A.G., U.S.), the Department of Cardiology, University Heart and Vascular Center Hamburg (P.K., T.T., N.B.), and the Institute of Medical Biometry and Epidemiology (A.-K.O., S.S., A.Z.), University Medical Center Hamburg-Eppendorf, and the German Center for Cardiovascular Research (DZHK) Partner Site Hamburg-Kiel-Lübeck (P.K., T.T., N.B.), Hamburg, the Department of Cardiology and Intensive Care Medicine, St. Vincenz Hospital Paderborn, Paderborn (A.G.), the Department of Neuroepidemiology, Institute for Medical Informatics, Biometry, and Epidemiology, University Duisburg-Essen, Essen (H.C.D.), and the Heart Center, Segeberger Kliniken, Bad Segeberg (M.B.) - all in Germany; the Institute of Cardiovascular Sciences (P.K.) and the Centre for Patient Reported Outcome Research, Institute of Applied Health Research, the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, and the NIHR Applied Research Collaboration West Midlands (M.C.), University of Birmingham, Birmingham, the Cardiovascular and Cell Sciences Research Institute, St. George's University of London, and Imperial College London, London (A.J.C.), the Cardiac Department, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford (K.R.), and Liverpool Centre for Cardiovascular Science at University of Liverpool, John Moores University, and Liverpool Heart and Chest Hospital, Liverpool (G.Y.H.L.) - all in the United Kingdom; Unità Operativa Complessa Cardiologia-Azienda Ospedale Università di Padova, Padua, Italy (E.B.); the Department of Medical Science, Uppsala University, Uppsala, and the Department of Cardiology, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro - both in Sweden (C.B.L.); the Department of Cardiology, Odense University Hospital, Odense, and the Department of Cardiology, Esbjerg Hospital-University Hospital of Southern Denmark, Esbjerg (A.B.), and the Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg (G.Y.H.L.) - all in Denmark; the Cardiology Department, Fernando Fonseca Hospital, Amadora, Portugal (N.C.); the Biostatistics Lab, School of Medicine, University of Crete (G.C.), and the Department of Cardiology, Heraklion University Hospital (E.S.), Heraklion, and the Biomedical Research Foundation Academy of Athens and Hygeia Hospitals Group, Athens (P.V.) - all in Greece; Medicine University Carol Davila, Colentina University Hospital, Bucharest, Romania (G.-A.D.); the Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam (J.R.G.), and the Departments of Cardiology and Physiology, Maastricht University, Maastricht (U.S.) - both in the Netherlands; the Department of Internal Medicine III, Cardiology and Angiology, Innsbruck Medical University, Innsbruck (W.D.), and the Department of Cardiology, Medical University of Graz, Graz (D.S.) - both in Austria; the National Institute of Cardiovascular Surgery, Academy of Medical Sciences of Ukraine, Kyiv (B.K.); the Department of Cardiology and Internal Disease, Medical University of Gdansk, Gdansk (A.L.), and the Department of Electrocardiology and Heart Failure, Leszek Giec Upper Silesian Medical Center, Katowice (R.S.) - both in Poland; the Cardiology Division, European Georges Pompidou Hospital, Paris (E.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); the Hospital Clinic, Universtitat de Barcelona, Barcelona, Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, and Centro de Investigacion Biomedica en Red Cardiovascular, Madrid - all in Spain (L.M.); the Department of Cardiology, University Hospital Antwerp, Edegem, Belgium (A.S.); the Cardiology Clinic, St. Anna University Hospital Sofia, Sofia Medical University, Sofia, Bulgaria (V.V.); and the Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic (D.W.).

Insights

Edoxaban did not significantly reduce stroke risk in patients with device-detected atrial high-rate episodes (AHREs). Anticoagulation with edoxaban increased the risk of death or major bleeding compared to placebo.

Area of Science:

  • Cardiology
  • Clinical Trials
  • Pharmacology

Background:

  • Device-detected atrial high-rate episodes (AHREs) are brief arrhythmias detected by pacemakers or defibrillators.
  • The clinical significance of AHREs and the need for anticoagulation in patients without documented atrial fibrillation remain unclear.

Purpose of the Study:

  • To investigate whether anticoagulation with edoxaban is effective and safe in patients with AHREs and at least one additional stroke risk factor.
  • To compare the incidence of cardiovascular events and bleeding between edoxaban and placebo groups.

Main Methods:

  • A randomized, double-blind, double-dummy trial involving 2536 patients aged 65 years or older with AHREs.
  • Patients received either edoxaban or placebo, with primary efficacy assessed by a composite of cardiovascular death, stroke, or systemic embolism.
  • Safety outcomes included all-cause death or major bleeding.

Main Results:

  • The trial was terminated early due to safety concerns and futility assessment.
  • Edoxaban did not significantly reduce the primary efficacy outcome (HR, 0.81; P=0.15).
  • Edoxaban significantly increased the risk of death or major bleeding (HR, 1.31; P=0.03), with low stroke incidence in both groups.

Conclusions:

  • Anticoagulation with edoxaban in patients with AHREs did not provide significant efficacy benefits.
  • Edoxaban use was associated with an increased risk of major bleeding and death.
  • The findings suggest that anticoagulation may not be warranted solely based on AHREs detected by devices.
Abstract

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