AIMS: Heart failure (HF) is a risk factor for major adverse events in atrial fibrillation (AF). Whether this risk persists on non-vitamin K antagonist oral anticoagulants (NOACs) and varies according to left ventricular ejection fraction (LVEF) is debated. METHODS AND RESULTS: We investigated the relation of HF in the ETNA-AF-Europe registry, a prospective, multicentre, observational study with an overall 4-year follow-up of edoxaban-treated AF patients. We report 2-year follow-up for ischaemic stroke/transient ischaemic attack (TIA)/systemic embolic events (SEE), major bleeding, and mortality. Of the 13 133 patients, 1854 (14.1%) had HF. Left ventricular ejection fraction was available for 82.4% of HF patients and was <40% in 671 (43.9%) and ≥40% in 857 (56.1%). Patients with HF were older, more often men, and had more comorbidities. Annualized event rates (AnERs) of any stroke/SEE were 0.86%/year and 0.67%/year in patients with and without HF. Compared with patients without HF, those with HF also had higher AnERs for major bleeding (1.73%/year vs. 0.86%/year) and all-cause death (8.30%/year vs. 3.17%/year). Multivariate Cox proportional models confirmed HF as a significant predictor of major bleeding [hazard ratio (HR) 1.65, 95% confidence interval (CI): 1.20-2.26] and all-cause death [HF with LVEF <40% (HR 2.42, 95% CI: 1.95-3.00) and HF with LVEF ≥40% (HR 1.80, 95% CI: 1.45-2.23)] but not of ischaemic stroke/TIA/SEE. CONCLUSION: Anticoagulated patients with HF at baseline featured higher rates of major bleeding and all-cause death, requiring optimized management and novel preventive strategies. NOAC treatment was similarly effective in reducing risk of ischaemic events in patients with or without concomitant HF.

Cardiac Thoracic and Vascular Department IRCCS Ospedale Policlinico San Martino Genova Italy

Cardiology Division Pisa University Hospital Pisa Italy

Czech Academy of Science Institute of Computer Sciences Prague Czech Republic

Daiichi Sankyo Europe GmbH Munich Germany

Department of Cardiology Medical University of Vienna Vienna Austria

Department of Cardiology University Clinic Hamburg Eppendorf University Heart and Vascular Centre Hamburg Eppendorf Buildung O50 Martinistrasse 52 20246 Hamburg Germany

Department of Cardiology University Heart and Vascular Centre Hamburg University Medical Centre Hamburg Eppendorf Hamburg Germany

Department of Immunochemistry Diagnostics University Hospital Pilsen Pilsen Czech Republic

Department of Internal Medicine University of Genova Genova Italy

Department of Medical and Surgical Sciences University of Bologna 40138 Bologna Italy

DZHK partner site Hamburg Kiel Luebeck Potsdamer Str 5810785 Berlin Germany

Fondazione Villa Serena per la Ricerca Pescara Italy

German Center for Cardiovascular Sciences partner site Hamburg Kiel Lübeck Germany

Institute of Cardiovascular Sciences University of Birmingham Birmingham UK

Unit of Cardiology IRCCS Azienda Ospedaliero Universitaria di Bologna 40138 Bologna Italy

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