title: Geographic variations in the PARADIGM-HF heart failure trial.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK john.mcmurray@glasgow.ac.uk.|Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Søren Lund
authors.initials: SL
authors.lastname: Kristensen
authors.affiliation: Emeritus Professor of Medicine, Universidad Nacional of Cordoba, Cordoba, Argentina john.mcmurray@glasgow.ac.uk.
authors.forename: Felipe
authors.initials: F
authors.lastname: Martinez
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK john.mcmurray@glasgow.ac.uk.
authors.forename: Pardeep S
authors.initials: PS
authors.lastname: Jhund
authors.affiliation: Guatemalan Heart Institute, Guatemala john.mcmurray@glasgow.ac.uk.
authors.forename: Juan Luis
authors.initials: JL
authors.lastname: Arango
authors.affiliation: 2nd Department of Medicine, Cardiovascular Medicine, General University Hospital and 1st Medical School, Charles University in Prague, Prague, Czech Republic john.mcmurray@glasgow.ac.uk.
authors.forename: Jan
authors.initials: J
authors.lastname: Bĕlohlávek
authors.affiliation: National Research Center for Preventive Medicine, Moscow, Russia john.mcmurray@glasgow.ac.uk.
authors.forename: Sergey
authors.initials: S
authors.lastname: Boytsov
authors.affiliation: Clinica Vesalio, Lima, Peru john.mcmurray@glasgow.ac.uk.
authors.forename: Walter
authors.initials: W
authors.lastname: Cabrera
authors.affiliation: Clinica Shaio, Bogota, Colombia john.mcmurray@glasgow.ac.uk.
authors.forename: Efrain
authors.initials: E
authors.lastname: Gomez
authors.affiliation: 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 john.mcmurray@glasgow.ac.uk.
authors.forename: Albert A
authors.initials: AA
authors.lastname: Hagège
authors.affiliation: First Affiliated Hospital with Nanjing Medical University, Nanjing, China john.mcmurray@glasgow.ac.uk.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Cardiology, Medicine, Khon Kaen University, Khon Kaen, Thailand john.mcmurray@glasgow.ac.uk.
authors.forename: Songsak
authors.initials: S
authors.lastname: Kiatchoosakun
authors.affiliation: Daegu Catholic University Hospital, Daegu, Korea john.mcmurray@glasgow.ac.uk.
authors.forename: Kee-Sik
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Venezuela Instituto Tropical Medicine Universidad Central Venezuela, Caracas, Venezuela john.mcmurray@glasgow.ac.uk.
authors.forename: Iván
authors.initials: I
authors.lastname: Mendoza
authors.affiliation: Azienda Ospedaliera Papa Giovanni XXIII, Cardiologia 1 - Scompenso e Trapianti di Cuore, Bergamo, Italy john.mcmurray@glasgow.ac.uk.
authors.forename: Michele
authors.initials: M
authors.lastname: Senni
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, and NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK john.mcmurray@glasgow.ac.uk.
authors.forename: Iain B
authors.initials: IB
authors.lastname: Squire
authors.affiliation: University of Medicine and Pharmacy Carol Davila - University and Emergency Hospital, Bucharest, Romania john.mcmurray@glasgow.ac.uk.
authors.forename: Dragos
authors.initials: D
authors.lastname: Vinereanu
authors.affiliation: Department of Cardiology, National University Heart Centre, Singapore john.mcmurray@glasgow.ac.uk.
authors.forename: Raymond Ching-Chiew
authors.initials: RC
authors.lastname: Wong
authors.affiliation: Novartis Pharmaceuticals, East Hanover, New Jersey, USA john.mcmurray@glasgow.ac.uk.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Gong
authors.affiliation: Novartis Pharmaceuticals, East Hanover, New Jersey, USA john.mcmurray@glasgow.ac.uk.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Lefkowitz
authors.affiliation: Novartis Pharmaceuticals, East Hanover, New Jersey, USA john.mcmurray@glasgow.ac.uk.
authors.forename: Adel R
authors.initials: AR
authors.lastname: Rizkala
authors.affiliation: Institut de Cardiologie de Montréal, Université de Montréal, Montreal, Canada john.mcmurray@glasgow.ac.uk.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Rouleau
authors.affiliation: Novartis Pharmaceuticals, East Hanover, New Jersey, USA john.mcmurray@glasgow.ac.uk.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Shi
authors.affiliation: Brigham and Women's Hospital, Boston, MA, USA john.mcmurray@glasgow.ac.uk.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.affiliation: University of Gothenburg, Gothenburg, Sweden john.mcmurray@glasgow.ac.uk.|National Heart and Lung Institute, Imperial College, London, UK.
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.affiliation: Medical University of South Carolina and Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA john.mcmurray@glasgow.ac.uk.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zile
authors.affiliation: Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX, USA john.mcmurray@glasgow.ac.uk.
authors.forename: Milton
authors.initials: M
authors.lastname: Packer
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK john.mcmurray@glasgow.ac.uk.
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
mesh_terms: D000368:Aged; D001208:Asia; D005060:Europe; D006333:Heart Failure; D006760:Hospitalization; D006801:Humans; D008875:Middle Aged
keywords: Clinical trial; Geographical variation; Heart failure; Prognosis; Treatment outcome