Scott D Solomon1, Adel R Rizkala2, Jianjian Gong2, Wenyan Wang2, Inder S Anand3, Junbo Ge4, Carolyn S P Lam5, Aldo P Maggioni6, Felipe Martinez7, Milton Packer8, Marc A Pfeffer9, Burkert Pieske10, Margaret M Redfield11, Jean L Rouleau12, Dirk J Van Veldhuisen13, Faiez Zannad14, Michael R Zile15, Akshay S Desai9, Victor C Shi2, Martin P Lefkowitz2, John J V McMurray16. 1. Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: ssolomon@bwh.harvard.edu. 2. Novartis, East Hanover, New Jersey. 3. University of Minnesota, Minneapolis, Minnesota. 4. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, Beijing, China. 5. National Heart Centre Singapore and Duke-National University of Singapore, Singapore. 6. ANMCO, Florence, Italy. 7. Universidad Nacional of Cordoba, Cordoba, Argentina. 8. Baylor University Medical Center, Dallas, Texas. 9. Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 10. Charité University Medicine, Berlin, Germany; German Heart Center, Berlin, Germany. 11. Mayo Clinic, Rochester, Minnesota. 12. Institut de Cardiologie de Montréal, Université de Montréal, Montreal, Canada. 13. University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. 14. Inserm CIC 1433 and Université de Lorraine, CHRU Nancy, France. 15. Medical University of South Carolina, Charleston, South Carolina; RHJ Department of Veterans Affairs Medical Center, Charleston, South Carolina. 16. BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland.
Abstract
OBJECTIVES: The PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction) trial is designed to determine the efficacy and safety of the angiotensin receptor neprilysin inhibitor sacubitril/valsartan compared with valsartan in patients with chronic heart failure and preserved ejection fraction (HFpEF). BACKGROUND:HFpEF is highly prevalent, associated with substantial morbidity and mortality, and in need of effective therapies that improve outcomes. The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan, which has been shown to benefit patients with heart failure (HF) and reduced ejection fraction, demonstrated favorable physiologic effects in a phase II HFpEF trial. METHODS: The PARAGON-HF trial is a randomized, double-blind, parallel group, active-controlled, event-driven trial comparing the long-term efficacy and safety of valsartan and sacubitril/valsartan in patients with chronic HFpEF (left ventricular ejection fraction ≥45%), New York Heart Association functional class II to IV symptoms, elevated natriuretic peptides, and evidence of structural heart disease. Before randomization, all patients entered sequential single-blind run-in periods to ensure tolerability of both drugs at half the target doses (i.e., valsartan titrated to 80 mg bid followed by sacubitril/valsartan 49/51 mg [100 mg] bid). The primary outcome is the composite of cardiovascular death and total (first and recurrent) HF hospitalizations. CONCLUSIONS: PARAGON-HF will determine whether sacubitril/valsartan is superior to angiotensin receptor blockade alone in patients with chronic symptomatic HFpEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).
RCT Entities:
OBJECTIVES: The PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction) trial is designed to determine the efficacy and safety of the angiotensin receptor neprilysin inhibitor sacubitril/valsartan compared with valsartan in patients with chronic heart failure and preserved ejection fraction (HFpEF). BACKGROUND: HFpEF is highly prevalent, associated with substantial morbidity and mortality, and in need of effective therapies that improve outcomes. The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan, which has been shown to benefit patients with heart failure (HF) and reduced ejection fraction, demonstrated favorable physiologic effects in a phase II HFpEF trial. METHODS: The PARAGON-HF trial is a randomized, double-blind, parallel group, active-controlled, event-driven trial comparing the long-term efficacy and safety of valsartan and sacubitril/valsartan in patients with chronic HFpEF (left ventricular ejection fraction ≥45%), New York Heart Association functional class II to IV symptoms, elevated natriuretic peptides, and evidence of structural heart disease. Before randomization, all patients entered sequential single-blind run-in periods to ensure tolerability of both drugs at half the target doses (i.e., valsartan titrated to 80 mg bid followed by sacubitril/valsartan 49/51 mg [100 mg] bid). The primary outcome is the composite of cardiovascular death and total (first and recurrent) HF hospitalizations. CONCLUSIONS: PARAGON-HF will determine whether sacubitril/valsartan is superior to angiotensin receptor blockade alone in patients with chronic symptomatic HFpEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart FailurePatients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).
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