Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction: Rationale and Design of the PARAGON-HF Trial

Scott D. Solomon, Adel R. Rizkala, Jianjian Gong, Wenyan Wang, Inder S. Anand, Junbo Ge, Carolyn S.P. Lam, Aldo P. Maggioni, Felipe Martinez, Milton Packer, Marc A. Pfeffer, Burkert Pieske, Margaret May Redfield, Jean L. Rouleau, Dirk J. Van Veldhuisen, Faiez Zannad, Michael R. Zile, Akshay S. Desai, Victor C. Shi, Martin P. LefkowitzJohn J.V. McMurray

Research output: Contribution to journalReview article

99 Citations (Scopus)

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)

Original languageEnglish (US)
Pages (from-to)471-482
Number of pages12
JournalJACC: Heart Failure
Volume5
Issue number7
DOIs
StatePublished - Jul 1 2017

Fingerprint

Neprilysin
Angiotensin Receptors
Heart Failure
Valsartan
Safety
Morbidity
Natriuretic Peptides
Mortality
Random Allocation
Stroke Volume
LCZ 696
Heart Diseases

Keywords

  • angiotensin receptor neprilysin inhibitor
  • heart failure with preserved ejection fraction
  • sacubitril
  • valsartan

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction : Rationale and Design of the PARAGON-HF Trial. / Solomon, Scott D.; Rizkala, Adel R.; Gong, Jianjian; Wang, Wenyan; Anand, Inder S.; Ge, Junbo; Lam, Carolyn S.P.; Maggioni, Aldo P.; Martinez, Felipe; Packer, Milton; Pfeffer, Marc A.; Pieske, Burkert; Redfield, Margaret May; Rouleau, Jean L.; Van Veldhuisen, Dirk J.; Zannad, Faiez; Zile, Michael R.; Desai, Akshay S.; Shi, Victor C.; Lefkowitz, Martin P.; McMurray, John J.V.

In: JACC: Heart Failure, Vol. 5, No. 7, 01.07.2017, p. 471-482.

Research output: Contribution to journalReview article

Solomon, SD, Rizkala, AR, Gong, J, Wang, W, Anand, IS, Ge, J, Lam, CSP, Maggioni, AP, Martinez, F, Packer, M, Pfeffer, MA, Pieske, B, Redfield, MM, Rouleau, JL, Van Veldhuisen, DJ, Zannad, F, Zile, MR, Desai, AS, Shi, VC, Lefkowitz, MP & McMurray, JJV 2017, '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, pp. 471-482. https://doi.org/10.1016/j.jchf.2017.04.013
Solomon, Scott D. ; Rizkala, Adel R. ; Gong, Jianjian ; Wang, Wenyan ; Anand, Inder S. ; Ge, Junbo ; Lam, Carolyn S.P. ; Maggioni, Aldo P. ; Martinez, Felipe ; Packer, Milton ; Pfeffer, Marc A. ; Pieske, Burkert ; Redfield, Margaret May ; Rouleau, Jean L. ; Van Veldhuisen, Dirk J. ; Zannad, Faiez ; Zile, Michael R. ; Desai, Akshay S. ; Shi, Victor C. ; Lefkowitz, Martin P. ; McMurray, John J.V. / Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction : Rationale and Design of the PARAGON-HF Trial. In: JACC: Heart Failure. 2017 ; Vol. 5, No. 7. pp. 471-482.
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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)",
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T1 - Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction

T2 - 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 May

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.

PY - 2017/7/1

Y1 - 2017/7/1

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)

AB - 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)

KW - angiotensin receptor neprilysin inhibitor

KW - heart failure with preserved ejection fraction

KW - sacubitril

KW - valsartan

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