Scott D Solomon1, Adel R Rizkala2, Martin P Lefkowitz2, Victor C Shi2, JianJian Gong2, Nagesh Anavekar3, Stefan D Anker4,5, Juan L Arango6, Jose L Arenas7, Dan Atar8, Turia Ben-Gal9, Sergey A Boytsov10, Chen-Huan Chen11, Vijay K Chopra12, John Cleland13,14,15, Josep Comin-Colet15, Hans-Dirk Duengen10, Luis E Echeverría Correa11, Gerasimos Filippatos16,17, Andreas J Flammer18, Michel Galinier19, Armando Godoy20,21,22, Eva Goncalvesova23, Stefan Janssens24, Tzvetana Katova25, Lars Køber26, Małgorzata Lelonek27, Gerard Linssen28, Lars H Lund29, Eileen O'Meara30, Béla Merkely31, Davor Milicic32, Byung-Hee Oh33, Sergio V Perrone34, Naresh Ranjith35, Yoshihiko Saito36, Jose F Saraiva37, Sanjiv Shah38, Petar M Seferovic39, Michele Senni40, Antonio S Sibulo41, David Sim42, Nancy K Sweitzer43, Jyrki Taurio44, Dragos Vinereanu45, Bojan Vrtovec46, Jiří Widimský47, Mehmet B Yilmaz48, Jingmin Zhou49, Robert Zweiker50, Inder S Anand51, Junbo Ge52, Carolyn S P Lam53, Aldo P Maggioni54, Felipe Martinez55, Milton Packer56, Marc A Pfeffer57, Burkert Pieske58, Margaret M Redfield59, Jean L Rouleau30, Dirk J Van Veldhuisen60, Faiez Zannad61, Michael R Zile62, John J V McMurray63. 1. Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.D.S., M.A.P.). ssolomon@bwh.harvard.edu. 2. Novartis Pharmaceuticals Corporation, East Hanover, NJ (V.C.S., A.R.R., J.J.G., M.P.L.). 3. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Australia (N.A.). 4. Division of Cardiology and Metabolism, Department of Cardiology (CVK) and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) Berlin, Charité Universitätsmedizin Berlin, Germany (S.D.A.). 5. Department of Cardiology and Pneumology, University of Göttingen Medical Center, Germany (S.D.A.). 6. Guatemalan Heart Institute (J.L. Arango). 7. Centro de Atención e Investigación Cardiovascular del Potosi SC and Hospital Ángeles San Luis, México (J.L. Arenas). 8. Department of Cardiology B, Oslo University Hospital, University of Oslo, Norway (D.A.). 9. Heart Failure Unit, Cardiology Department, Rabin Medical Center, Petah Tikva, Israel (T.B.-G.). 10. National Research Center for Cardiology of the Ministry of Health of the Russian Federation, Moscow, Russia (S.A.B.). 11. Department of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China (C.-H.C.). 12. Heart Failure Unit, Medanta Medicity, Gurugram, Haryana, India (V.K.C.). 13. Robertson Centre for Biostatistics and Clinical Trials, Institute of Health and Wellbeing (J.C.). 14. University of Glasgow, United Kingdom. National Heart and Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College, London, United Kingdom (J.C.). 15. Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital and Institut d'Investigació Biomèdica de Bellvitge, University of Barcelona, Spain (J.C.-C.). 16. Attikon University Hospital, National and Kapodistrian University of Athens, Greece (G.F.). 17. School of Medicine, University of Cyprus, Greece (G.F.). 18. Department of Cardiology, University Heart Center Zurich, University Hospital Zurich, Switzerland (A.J.F.). 19. Department of Cardiology, Rangueil University Hospital, Toulouse, France (M.G.). 20. Universidad Nacional Mayor de San Marcos, Lima, Perú (A.G.). 21. Instituto Nacional Cardiovascular INCOR, Lima, Perú (A.G.). 22. Scientia Clinical and Epidemiological Research Institute, Trujillo, Perú (A.G.). 23. Department of Heart Failure/Transplantation, National Cardiovascular Institute, Bratislava, Slovakia (E.G.). 24. Department of Cardiology, University Hospitals Leuven, Belgium (S.J.). 25. Clinic of Cardiology, National Cardiology Hospital, Sofia, Bulgaria (T.K.). 26. Department of Cardiology, Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark (L.K.). 27. Department of Noninvasive Cardiology, Medical University of Lodz, Poland (M.L.). 28. Department of Cardiology, Hospital Group Twente, Almelo and Hengelo, The Netherlands (G.L.). 29. Department of Medicine, Karolinska Institutet, and Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden (L.H.L.). 30. Institut de Cardiologie de Montréal, Université de Montréal, Québec, Canada (E.O.M., J.L.R.). 31. Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.). 32. Department of Cardiovascular Diseases, University Hospital Center Zagreb, Croatia (D.M.). 33. Seoul National University Hospital, Seoul National University College of Medicine, Korea (B.-H.O.). 34. Instituto FLENI, Buenos Aires, Argentina (S.V.P.). 35. Department of Cardiology, City Hospital, Durban, South Africa (N.R.). 36. First Department of Internal Medicine, Nara Medical University, Kashihara, Japan (Y.S.). 37. Disciplina de Cardiologia Faculdade de Medicina, Pontifícia Universidade Católica de Campinas, Sao Paulo, Brazil (J.F.K.S.). 38. Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.S.). 39. Department of Cardiology, University of Belgrade School of Medicine, Belgrade University Medical Center, Serbia (P.M.S.). 40. Cardiology Division, Cardiovascular Department, Hospital Papa Giovanni XXIII, Bergamo, Italy (M.S.). 41. St Luke's Heart Institute, St. Luke's Medical Center, Taguig, Philippines (A.S.S.). 42. Department of Cardiology, National Heart Centre Singapore (D.S.). 43. Sarver Heart Center, University of Arizona College of Medicine, Tucson (N.K.S.). 44. Department of Cardiology, Tampere University Hospital, Finland (J.T.). 45. University of Medicine and Pharmacy Carol Davila, University and Emergency Hospital of Bucharest, Romania (D.V.). 46. University Medical Centre, Ljubljana, Slovenia (B.V.). 47. First Faculty of Medicine, Charles University Prague, Czech Republic (J.W.). 48. Department of Cardiology, Faculty of Medicine, Cumhuriyet University, Sivas, Turkey (M.B.Y.). 49. Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China (J.Z.). 50. Department of Cardiology, Medical University Graz, Austria (R.Z.). 51. Department of Medicine, VA Medical Center and University of Minnesota, Minneapolis (I.S.A.). 52. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, China (J.G.). 53. National Heart Centre Singapore and Duke-National University of Singapore (C.S.P.L.). 54. Associazione Nazionale Medici Cardiologi Ospedalieri, Florence, Italy (A.P.M.). 55. Universidad Nacional of Cordoba, Argentina (F.M.). 56. Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX (M.P.). 57. Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.D.S., M.A.P.). 58. Department of Internal Medicine, Cardiology Charité, Universitaetsmedizin Berlin, Campus Virchow Klinikum Berlin, Germany (B.P., H.-D.D.). 59. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (M.M.R.). 60. University Medical Center Groningen, University of Groningen, The Netherlands (D.J.V.V.). 61. Inserm CIC 1433 and Université de Lorraine, Centre Hospitalier Ré gional Universitaire, Nancy, France (F.Z.). 62. Medical University of South Carolina and Ralph H. Johnson Veterans Administration Medical Center, Charleston (M.R.Z.). 63. British Heart Foundation Cardiovascular Research Centre (J.J.V.M.).
Abstract
BACKGROUND: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. METHODS AND RESULTS: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), β-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464-1610), and structural heart disease. CONCLUSIONS: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711.
RCT Entities:
BACKGROUND: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. METHODS AND RESULTS: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), β-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464-1610), and structural heart disease. CONCLUSIONS: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711.