Alvin Chandra1, Muthiah Vaduganathan1, Eldrin F Lewis1, Brian L Claggett1, Adel R Rizkala2, Wenyan Wang2, Martin P Lefkowitz2, Victor C Shi2, Inder S Anand3, Junbo Ge4, Carolyn S P Lam5, Aldo P Maggioni6, Felipe Martinez7, Milton Packer8, Marc A Pfeffer1, Burkert Pieske9, Margaret M Redfield10, Jean L Rouleau11, Dirk J Van Veldhuisen12, Faiez Zannad13, Michael R Zile14, John J V McMurray15, Scott D Solomon16. 1. Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 2. Novartis Pharmaceutical Corporation, East Hanover, New Jersey. 3. Department of Medicine, University of Minnesota, Minneapolis, Minnesota. 4. Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China. 5. National Heart Centre Singapore, Duke-National University of Singapore Medical School, Singapore; George Institute for Global Health, University of New South Wales, Sydney, Australia. 6. ANMCO Research Center, Florence, Italy. 7. Universidad Nacional of Cordoba, Cordoba, Argentina. 8. Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas; Imperial College London, London, United Kingdom. 9. Department of Internal Medicine, Cardiology Charité, Universitaetsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany; German Heart Center, Berlin, Germany. 10. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota. 11. Institut de Cardiologie de Montréal, Université de Montréal, Montreal, Canada. 12. University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. 13. Inserm CIC 1433, French Clinical Research Infrastructure Network, Investigation Network Initiative Cardiovascular and Renal Clinical Trialists, Centre Hospitalier Régionale Universitaire de Nancy, Université de Lorraine, Nancy, France. 14. Medical University of South Carolina, Charleston, South Carolina; Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina. 15. British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland. 16. Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: ssolomon@bwh.harvard.edu.
Abstract
OBJECTIVES: This study sought to describe baseline health-related quality of life (HRQL) in the PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF) trial, the largest heart failure with preserved ejection fraction (HFpEF) trial to date. BACKGROUND: There are limited data characterizing HRQL in patients with HFpEF using validated metrics. METHODS: The PARAGON-HF trial randomized symptomatic patients with HFpEF (≥45%) ≥50 years of age to eithersacubitril/valsartan or valsartan. The study reports comprehensive baseline HRQL using Kansas City Cardiomyopathy Questionnaire (KCCQ) administered at randomization after active run-in period. The study then compares baseline HRQL with patients with heart failure with reduced ejection fraction (HFrEF) (≤40%) enrolled in the PARADIGM-HF (Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Forward multivariable stepwise regression modeling was performed separately in both trials to identify independent clinical correlates of KCCQ-Overall Summary (KCCQ-OS) score. PARADIGM-HF trial patients <50 years of age were excluded to enable comparison. RESULTS: In the PARAGON-HF trial, 4,735 of 4,822 patients (mean age 73 ± 8 years; 48% men) completed baseline KCCQ at randomization. Mean KCCQ-OS score was 71. Women had worse mean KCCQ-OS score than men did. Patients in the PARAGON-HF trial reported lower KCCQ scores in nearly all domains when compared with the PARADIGM-HF trial (KCCQ-OS score 71 ± 19 vs. 73 ± 19; p < 0.001). The strongest independent clinical correlates of adverse HRQL in both the PARAGON-HF and PARADIGM-HF trials were New York Heart Association functional class, female gender, lower extremity edema, body mass index, angina, dyspnea, and paroxysmal nocturnal dyspnea. After accounting for these clinical correlates of adverse HRQL that were common to both HFpEF and HFrEF patients, KCCQ-OS score did not differ significantly. CONCLUSIONS:HRQL was largely worse in women and was similar in HFpEF and HFrEF after accounting for variation in demographics, functional status, and symptom burden. (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF [PARAGON-HF] NCT01920711; Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255).
RCT Entities:
OBJECTIVES: This study sought to describe baseline health-related quality of life (HRQL) in the PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF) trial, the largest heart failure with preserved ejection fraction (HFpEF) trial to date. BACKGROUND: There are limited data characterizing HRQL in patients with HFpEF using validated metrics. METHODS: The PARAGON-HF trial randomized symptomatic patients with HFpEF (≥45%) ≥50 years of age to either sacubitril/valsartan or valsartan. The study reports comprehensive baseline HRQL using Kansas City Cardiomyopathy Questionnaire (KCCQ) administered at randomization after active run-in period. The study then compares baseline HRQL with patients with heart failure with reduced ejection fraction (HFrEF) (≤40%) enrolled in the PARADIGM-HF (Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Forward multivariable stepwise regression modeling was performed separately in both trials to identify independent clinical correlates of KCCQ-Overall Summary (KCCQ-OS) score. PARADIGM-HF trial patients <50 years of age were excluded to enable comparison. RESULTS: In the PARAGON-HF trial, 4,735 of 4,822 patients (mean age 73 ± 8 years; 48% men) completed baseline KCCQ at randomization. Mean KCCQ-OS score was 71. Women had worse mean KCCQ-OS score than men did. Patients in the PARAGON-HF trial reported lower KCCQ scores in nearly all domains when compared with the PARADIGM-HF trial (KCCQ-OS score 71 ± 19 vs. 73 ± 19; p < 0.001). The strongest independent clinical correlates of adverse HRQL in both the PARAGON-HF and PARADIGM-HF trials were New York Heart Association functional class, female gender, lower extremity edema, body mass index, angina, dyspnea, and paroxysmal nocturnal dyspnea. After accounting for these clinical correlates of adverse HRQL that were common to both HFpEF and HFrEF patients, KCCQ-OS score did not differ significantly. CONCLUSIONS: HRQL was largely worse in women and was similar in HFpEF and HFrEF after accounting for variation in demographics, functional status, and symptom burden. (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF [PARAGON-HF] NCT01920711; Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255).
Authors: Vittal Hejjaji; Yuanyuan Tang; Theresa Coles; Philip G Jones; Bryce B Reeve; Robert J Mentz; Erica S Spatz; Shannon M Dunlay; Brittany Caldwell; Anindita Saha; Michelle E Tarver; Andy Tran; Krishna K Patel; Debra Henke; Ileana L Piña; John A Spertus Journal: Circ Heart Fail Date: 2021-09-01 Impact factor: 10.447
Authors: Lauren Gilstrap; Jonathan S Skinner; Barbara Gladders; A James O'Malley; Amber E Barnato; Anna N A Tosteson; Andrea M Austin Journal: Circ Cardiovasc Qual Outcomes Date: 2020-03-09