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Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction: Rationale and Design of the PARAGON-HF Trial.
JACC Heart Fail 2017; 5(7):471-482JH

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).

Authors+Show Affiliations

Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: ssolomon@bwh.harvard.edu.Novartis, East Hanover, New Jersey.Novartis, East Hanover, New Jersey.Novartis, East Hanover, New Jersey.University of Minnesota, Minneapolis, Minnesota.Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, Beijing, China.National Heart Centre Singapore and Duke-National University of Singapore, Singapore.ANMCO, Florence, Italy.Universidad Nacional of Cordoba, Cordoba, Argentina.Baylor University Medical Center, Dallas, Texas.Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Charité University Medicine, Berlin, Germany; German Heart Center, Berlin, Germany.Mayo Clinic, Rochester, Minnesota.Institut de Cardiologie de Montréal, Université de Montréal, Montreal, Canada.University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.Inserm CIC 1433 and Université de Lorraine, CHRU Nancy, France.Medical University of South Carolina, Charleston, South Carolina; RHJ Department of Veterans Affairs Medical Center, Charleston, South Carolina.Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Novartis, East Hanover, New Jersey.Novartis, East Hanover, New Jersey.BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland.

Pub Type(s)

Journal Article
Review
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28662936

Citation

Solomon, Scott D., et al. "Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction: Rationale and Design of the PARAGON-HF Trial." JACC. Heart Failure, vol. 5, no. 7, 2017, pp. 471-482.
Solomon SD, Rizkala AR, Gong J, et al. Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction: Rationale and Design of the PARAGON-HF Trial. JACC Heart Fail. 2017;5(7):471-482.
Solomon, S. D., Rizkala, A. R., Gong, J., Wang, W., Anand, I. S., Ge, J., ... McMurray, J. J. V. (2017). Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction: Rationale and Design of the PARAGON-HF Trial. JACC. Heart Failure, 5(7), pp. 471-482. doi:10.1016/j.jchf.2017.04.013.
Solomon SD, et al. Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction: Rationale and Design of the PARAGON-HF Trial. JACC Heart Fail. 2017;5(7):471-482. PubMed PMID: 28662936.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction: Rationale and Design of the PARAGON-HF Trial. AU - Solomon,Scott D, AU - Rizkala,Adel R, AU - Gong,Jianjian, AU - Wang,Wenyan, AU - Anand,Inder S, AU - Ge,Junbo, AU - Lam,Carolyn S P, AU - Maggioni,Aldo P, AU - Martinez,Felipe, AU - Packer,Milton, AU - Pfeffer,Marc A, AU - Pieske,Burkert, AU - Redfield,Margaret M, AU - Rouleau,Jean L, AU - Van Veldhuisen,Dirk J, AU - Zannad,Faiez, AU - Zile,Michael R, AU - Desai,Akshay S, AU - Shi,Victor C, AU - Lefkowitz,Martin P, AU - McMurray,John J V, Y1 - 2017/06/26/ PY - 2017/01/13/received PY - 2017/04/03/revised PY - 2017/04/21/accepted PY - 2017/7/1/entrez PY - 2017/7/1/pubmed PY - 2018/4/18/medline KW - angiotensin receptor neprilysin inhibitor KW - heart failure with preserved ejection fraction KW - sacubitril KW - valsartan SP - 471 EP - 482 JF - JACC. Heart failure JO - JACC Heart Fail VL - 5 IS - 7 N2 - 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). SN - 2213-1787 UR - https://www.unboundmedicine.com/medline/citation/28662936/Angiotensin_Receptor_Neprilysin_Inhibition in_Heart_Failure_With_Preserved Ejection_Fraction:_Rationale_and_Design_of_the_PARAGON_HF_Trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-1779(17)30319-0 DB - PRIME DP - Unbound Medicine ER -