AIMS: Patients with atrial fibrillation (AF) treated with oral anticoagulation still suffer from cardiovascular complications including cardiovascular death, stroke, and major bleeding. To identify risk factors for predicting stroke and bleeding outcomes in anticoagulated patients, we assessed 2-year outcomes in patients with AF treated with edoxaban in routine care. We also report the age-adjusted risk predictors of clinical outcomes. METHODS AND RESULTS: The Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular Atrial Fibrillation (ETNA-AF) Europe (NCT02944019) is a prospective, multi-centre, post-authorisation, observational study with an overall 4-year follow-up conducted in 825 centres enrolling edoxaban-treated patients in 10 European countries. Of the 13 133 patients with AF (mean age: 73.6 ± 9.5 years), 5682 (43.3%) were female. At the 2-year follow-up, 9017/13 133 patients were still on edoxaban; 1830 discontinued treatment including 937 who died (annualised event rate of all-cause death was 3.87%). 518 (2.14%) patients died of cardiovascular causes; 234 (0.97%) experienced major bleeding and 168 (0.70%) experienced stroke or systemic embolic events (SEE). Intracranial haemorrhage was noted in 49 patients (0.20%). History of transient ischaemic attack (TIA) at baseline was the strongest predictor of ischaemic stroke or SEE (Wald χ2: 73.63; P < 0.0001). Low kidney function at baseline was the strongest predictor of major bleeding (Wald χ2: 30.68; P < 0.0001). History of heart failure (HF) was the strongest predictor of all-cause (Wald χ2: 146.99; P < 0.0001) and cardiovascular death (Wald χ2: 100.38; P < 0.0001). CONCLUSION: Patients treated with edoxaban in ETNA-AF-Europe reported low 2-year event rates in unselected AF patients. Prior stroke, reduced kidney function, and HF identify patients at high risk of stroke, bleeding and all-cause/cardiovascular death, respectively.

Amsterdam Cardiovascular Sciences Heart Failure and Arrhythmias 1105 AZ Amsterdam the Netherlands

Amsterdam UMC location University of Amsterdam Cardiology Meibergrdreef 9 1105 AZ Amsterdam the Netherlands

AP HM Aix Marseille University Hospital Timone Cardiologie Rythmologie 264 rue Saint Pierre 13005 Marseille France

Cardiological Intensive Care Unit Cardiology Service Hospital Universitario La Paz IDIPAZ CIBERCV 28046 Madrid Spain

Chair of Cardiology and Vascular Medicine University of Munster Schlossplatz 2 48149 Munster Germany

Daiichi Sankyo Europe GmbH Zielstattstr 48 81379 Munich Germany

Department of Cardiology and Invasive Electrophysiology Heart Clinic Hirslanden Witellikerstrasse 40 8032 Zürich Switzerland

Department of Cardiology Centro Hospitalar e Universitario de Coimbra Praceta Mota Pinto 3000 075 Coimbra Portugal

Department of Cardiology Royal Free London NHS Foundation Trust Pond Street London NW3 2QG UK

Department of Cardiology University Heart and Vascular Centre Hamburg University Medical Centre Hamburg Eppendorf Martinistraße 52 20246 Hamburg Germany

Department of Economics Universite Paris Dauphine PSL Research University LEDa LEGOS 75775 Paris France

Department of Neurology HRB Stroke Clinical Trials Network Ireland University College Dublin Mater Misericordiae University Hospital Eccles St Northside D07 R2WY Dublin Ireland

Department of Statistical Modelling Institute of Computer Science of the Czech Academy of Sciences Pod Vodarenskou vezi 271 2 182 07 Prague Czech Republic

Department of Surgical Medical Molecular Pathology and Critical Care Medicine University of Pisa 1st Division of Cardiology Pisa University Hospital 56124 Pisa Italy; and Fondazione VillaSerena per la Ricerca Città Sant'Angelo Pescara Italy

Diagnostic and Therapeutic Heart Center Kappelistr 35 8002 Zurich Switzerland

German Center for Cardiovascular Sciences partner site Hamburg Kiel Lübeck Germany

Heart Rhythm Management Centre Postgraduate Program in Cardiac Electrophysiology and Pacing Vrije Universiteit Brussel Universitair Ziekenhuis Brussel Laarbeeklaan 101 1090 Jette Brussels Belgium

Institute for Cardiometabolic Diseases Karl Landsteiner Society 3100 St Polten Austria

Institute of Cardiovascular Sciences University of Birmingham IBR 136 Wolfson Drive Birmingham B15 2TT UK

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