Søren L Kristensen1, Lars Køber1, Pardeep S Jhund1, Scott D Solomon1, John Kjekshus1, Robert S McKelvie1, Michael R Zile1, Christopher B Granger1, John Wikstrand1, Michel Komajda1, Peter E Carson1, Marc A Pfeffer1, Karl Swedberg1, Hans Wedel1, Salim Yusuf1, John J V McMurray2. 1. From the BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom (S.L.K., P.S.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark (L.K.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (S.D.S., M.A.P.); the Department of Cardiology, Rikshospitalet, University of Oslo, Oslo, Norway (J.K.); Hamilton Health Sciences, McMaster University, Hamilton, ON, Canada (R.S.M., S.Y.); Ralph H. Johnsons Veterans Affairs Medical Center and Medical University of South Carolina, Charleston, SC (M.R.Z.); Duke Clinical Research Institute, Duke University Medical Centre, Durham, NC (C.B.G.); Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden (J.W.); Université Paris 6 and Hospital Pitié-Salpétrière, Paris, France (M.K.); Georgetown University and Washington DC Veterans Affairs Medical Center, Washington, DC (P.E.C.); Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden (K.S.); and Nordic School of Public Health, Gothenburg, Sweden (H.W.). 2. From the BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom (S.L.K., P.S.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark (L.K.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (S.D.S., M.A.P.); the Department of Cardiology, Rikshospitalet, University of Oslo, Oslo, Norway (J.K.); Hamilton Health Sciences, McMaster University, Hamilton, ON, Canada (R.S.M., S.Y.); Ralph H. Johnsons Veterans Affairs Medical Center and Medical University of South Carolina, Charleston, SC (M.R.Z.); Duke Clinical Research Institute, Duke University Medical Centre, Durham, NC (C.B.G.); Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden (J.W.); Université Paris 6 and Hospital Pitié-Salpétrière, Paris, France (M.K.); Georgetown University and Washington DC Veterans Affairs Medical Center, Washington, DC (P.E.C.); Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden (K.S.); and Nordic School of Public Health, Gothenburg, Sweden (H.W.). john.mcmurray@glasgow.ac.uk.
Abstract
BACKGROUND: International geographic differences in outcomes may exist for clinical trials of heart failure and reduced ejection fraction (HF-REF), but there are few data for those with preserved ejection fraction (HF-PEF). METHODS AND RESULTS: We analyzed outcomes by international geographic region in the Irbesartan in Heart Failure with Preserved systolic function trial (I-Preserve), the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved trial, the CHARM-Alternative and CHARM-Added HF-REF trials, and the Controlled Rosuvastatin Multinational Trial in HF-REF (CORONA). Crude rates of heart failure hospitalization varied by geographic region, and more so for HF-PEF than for HF-REF. Rates in patients with HF-PEF were highest in the United States/Canada (HF hospitalization rate 7.6 per 100 patient-years in I-Preserve; 8.8 in CHARM-Preserved), intermediate in Western Europe (4.8/100 and 4.7/100), and lowest in Eastern Europe/Russia (3.3/100 and 2.8/100). The difference between the United States/Canada versus Eastern Europe/Russia persisted after adjustment for key prognostic variables: adjusted hazard ratios 1.34 (95% confidence interval, 1.01-1.74; P=0.04) in I-Preserve and 1.85 (95% confidence interval, 1.17-2.91; P=0.01) in CHARM-Preserved. In HF-REF, rates of HF hospitalization were slightly lower in Western Europe compared with other regions. For both HF-REF and HF-PEF, there were few regional differences in rates of all-cause or cardiovascular mortality. CONCLUSIONS: The differences in event rates observed suggest there is international geographic variation in 1 or more of the definition and diagnosis of HF-PEF, the risk profile of patients enrolled, and the threshold for hospitalization, which has implications for the conduct of future global trials.
RCT Entities:
BACKGROUND: International geographic differences in outcomes may exist for clinical trials of heart failure and reduced ejection fraction (HF-REF), but there are few data for those with preserved ejection fraction (HF-PEF). METHODS AND RESULTS: We analyzed outcomes by international geographic region in the Irbesartan in Heart Failure with Preserved systolic function trial (I-Preserve), the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved trial, the CHARM-Alternative and CHARM-Added HF-REF trials, and the Controlled Rosuvastatin Multinational Trial in HF-REF (CORONA). Crude rates of heart failure hospitalization varied by geographic region, and more so for HF-PEF than for HF-REF. Rates in patients with HF-PEF were highest in the United States/Canada (HF hospitalization rate 7.6 per 100 patient-years in I-Preserve; 8.8 in CHARM-Preserved), intermediate in Western Europe (4.8/100 and 4.7/100), and lowest in Eastern Europe/Russia (3.3/100 and 2.8/100). The difference between the United States/Canada versus Eastern Europe/Russia persisted after adjustment for key prognostic variables: adjusted hazard ratios 1.34 (95% confidence interval, 1.01-1.74; P=0.04) in I-Preserve and 1.85 (95% confidence interval, 1.17-2.91; P=0.01) in CHARM-Preserved. In HF-REF, rates of HF hospitalization were slightly lower in Western Europe compared with other regions. For both HF-REF and HF-PEF, there were few regional differences in rates of all-cause or cardiovascular mortality. CONCLUSIONS: The differences in event rates observed suggest there is international geographic variation in 1 or more of the definition and diagnosis of HF-PEF, the risk profile of patients enrolled, and the threshold for hospitalization, which has implications for the conduct of future global trials.
Authors: Jacob P Kelly; Robert J Mentz; Alexandre Mebazaa; Adriaan A Voors; Javed Butler; Lothar Roessig; Mona Fiuzat; Faiez Zannad; Bertram Pitt; Christopher M O'Connor; Carolyn S P Lam Journal: J Am Coll Cardiol Date: 2015-04-28 Impact factor: 24.094
Authors: Andrew P Ambrosy; Adrian F Hernandez; Paul W Armstrong; Javed Butler; Allison Dunning; Justin A Ezekowitz; G Michael Felker; Stephen J Greene; Padma Kaul; John J McMurray; Marco Metra; Christopher M O'Connor; Shelby D Reed; Phillip J Schulte; Randall C Starling; W H Wilson Tang; Adriaan A Voors; Robert J Mentz Journal: Eur J Heart Fail Date: 2015-10-14 Impact factor: 15.534