AIMS: The globalization of clinical trials has highlighted geographic variations in patient characteristics, event rates, and treatment effects. We investigated these further in PARADIGM-HF, the largest and most globally representative trial in heart failure (HF) to date. METHODS AND RESULTS: We looked at five regions: North America (NA) 602 (8%), Western Europe (WE) 1680 (20%), Central/Eastern Europe/Russia (CEER) 2762 (33%), Latin America (LA) 1433 (17%), and Asia-Pacific (AP) 1487 (18%). Notable differences included: WE patients (mean age 68 years) and NA (65 years) were older than AP (58 years) and LA (63 years) and had more coronary disease; NA and CEER patients had the worst signs, symptoms, and functional status. North American patients were the most likely to have a defibrillating-device (54 vs. 2% AP) and least likely prescribed a mineralocorticoid receptor antagonist (36 vs. 65% LA). Other evidence-based therapies were used most frequently in NA and WE. Rates of the primary composite outcome of cardiovascular (CV) death or HF hospitalization (per 100 patient-years) varied among regions: NA 13.6 (95% CI 11.7-15.7) WE 9.6 (8.6-10.6), CEER 12.3 (11.4-13.2), LA 11.2 (10.0-12.5), and AP 12.5 (11.3-13.8). After adjustment for prognostic variables, relative to NA, the risk of CV death was higher in LA and AP and the risk of HF hospitalization lower in WE. The benefit of sacubitril/valsartan was consistent across regions. CONCLUSION: There were many regional differences in PARADIGM-HF, including in age, symptoms, comorbidity, background therapy, and event-rates, although these did not modify the benefit of sacubitril/valsartan. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.

1st Affiliated Hospital with Nanjing Medical University Nanjing China

2nd Department of Medicine Cardiovascular Medicine General University Hospital and 1st Medical School Charles University Prague Prague Czech Republic

Assistance Publique Hôpitaux de Paris Hôpital Européen Georges Pompidou Département de Cardiologie ; Paris Descartes University Sorbonne Paris Cité ; INSERM U970 Paris Cardiovascular Research Center Paris France

Azienda Ospedaliera Papa Giovanni XXIII Cardiologia 1 Scompenso e Trapianti di Cuore Bergamo Italy

Baylor Heart and Vascular Institute Baylor University Medical Center Dallas TX USA

BHF Glasgow Cardiovascular Research Centre Institute of Cardiovascular and Medical Sciences University of Glasgow Glasgow G12 8TA UK

Brigham and Women's Hospital Boston MA USA

Cardiology Medicine Khon Kaen University Khon Kaen Thailand

Clinica Shaio Bogota Colombia

Clinica Vesalio Lima Peru

Daegu Catholic University Hospital Daegu Korea

Department of Cardiology National University Heart Centre Singapore

Department of Cardiology Rigshospitalet Copenhagen Denmark

Department of Cardiovascular Sciences University of Leicester and NIHR Cardiovascular Biomedical Research Unit Glenfield Hospital Leicester UK

Emeritus Professor of Medicine Universidad Nacional of Cordoba Cordoba Argentina

Guatemalan Heart Institute Guatemala

Institut de Cardiologie de Montréal Université de Montréal Montreal Canada

Medical University of South Carolina and Ralph H Johnson Veterans Affairs Medical Center Charleston SC USA

National Heart and Lung Institute Imperial College London UK

National Research Center for Preventive Medicine Moscow Russia

Novartis Pharmaceuticals East Hanover New Jersey USA

University of Gothenburg Gothenburg Sweden

University of Medicine and Pharmacy Carol Davila University and Emergency Hospital Bucharest Romania

Venezuela Instituto Tropical Medicine Universidad Central Venezuela Caracas Venezuela

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ClinicalTrials.gov
NCT01035255