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Angiotensin Receptor-Neprilysin Inhibition Based on History of Heart Failure and Use of Renin-Angiotensin System Antagonists.

Publication ,  Journal Article
Ambrosy, AP; Braunwald, E; Morrow, DA; DeVore, AD; McCague, K; Meng, X; Duffy, CI; Rocha, R; Velazquez, EJ; PIONEER-HF Investigators,
Published in: J Am Coll Cardiol
September 1, 2020

BACKGROUND: The PIONEER-HF (comParIson Of sacubitril/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode) trial demonstrated the efficacy and safety of sacubitril/valsartan (S/V) in stabilized patients with acute decompensated heart failure (HF) and reduced ejection fraction. OBJECTIVES: The study sought to determine whether and how prior HF history and treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) affected the results. METHODS: The PIONEER-HF trial was a prospective, multicenter, double-blind, randomized clinical trial enrolling 881 patients with an ejection fraction ≤40%. Patients were randomly assigned 1:1 to in-hospital initiation of S/V (n = 440) versus enalapril (n = 441). Pre-specified subgroup analyses were performed based on prior HF history (i.e., de novo HF vs. worsening chronic HF) and treatment with an ACE inhibitor or ARB (i.e., ACE inhibitor or ARB-yes vs. ACE inhibitor or ARB-no) at admission. RESULTS: At enrollment, 303 (34%) patients presented with de novo HF and 576 (66%) patients with worsening chronic HF. A total of 421 (48%) patients had been treated with an ACE inhibitor or ARB, while 458 (52%) had not been treated with an ACE inhibitor or ARB. N-terminal pro-B-type natriuretic peptide declined significantly in all 4 subgroups (p < 0.001), with greater decreases in the S/V versus the enalapril arm (p < 0.001). There was no interaction between prior HF history (p = 0.350) or ACE inhibitor or ARB treatment (p = 0.880) and the effect of S/V versus enalapril on cardiovascular death or rehospitalization for HF. The incidences of adverse events were comparable between S/V and enalapril across all 4 subgroups. CONCLUSIONS: Among patients admitted for acute decompensated HF, S/V was safe and well tolerated, led to a significantly greater reduction in N-terminal pro-B-type natriuretic peptide, and improved clinical outcomes compared with enalapril irrespective of previous HF history or ACE inhibitor or ARB treatment. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890).

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Published In

J Am Coll Cardiol

DOI

EISSN

1558-3597

Publication Date

September 1, 2020

Volume

76

Issue

9

Start / End Page

1034 / 1048

Location

United States

Related Subject Headings

  • Valsartan
  • Tetrazoles
  • Renin-Angiotensin System
  • Receptors, Angiotensin
  • Prospective Studies
  • Neprilysin
  • Middle Aged
  • Male
  • Humans
  • Heart Failure
 

Citation

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ICMJE
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Ambrosy, A. P., Braunwald, E., Morrow, D. A., DeVore, A. D., McCague, K., Meng, X., … PIONEER-HF Investigators, . (2020). Angiotensin Receptor-Neprilysin Inhibition Based on History of Heart Failure and Use of Renin-Angiotensin System Antagonists. J Am Coll Cardiol, 76(9), 1034–1048. https://doi.org/10.1016/j.jacc.2020.06.073
Ambrosy, Andrew P., Eugene Braunwald, David A. Morrow, Adam D. DeVore, Kevin McCague, Xiangyi Meng, Carol I. Duffy, Ricardo Rocha, Eric J. Velazquez, and Eric J. PIONEER-HF Investigators. “Angiotensin Receptor-Neprilysin Inhibition Based on History of Heart Failure and Use of Renin-Angiotensin System Antagonists.J Am Coll Cardiol 76, no. 9 (September 1, 2020): 1034–48. https://doi.org/10.1016/j.jacc.2020.06.073.
Ambrosy AP, Braunwald E, Morrow DA, DeVore AD, McCague K, Meng X, et al. Angiotensin Receptor-Neprilysin Inhibition Based on History of Heart Failure and Use of Renin-Angiotensin System Antagonists. J Am Coll Cardiol. 2020 Sep 1;76(9):1034–48.
Ambrosy, Andrew P., et al. “Angiotensin Receptor-Neprilysin Inhibition Based on History of Heart Failure and Use of Renin-Angiotensin System Antagonists.J Am Coll Cardiol, vol. 76, no. 9, Sept. 2020, pp. 1034–48. Pubmed, doi:10.1016/j.jacc.2020.06.073.
Ambrosy AP, Braunwald E, Morrow DA, DeVore AD, McCague K, Meng X, Duffy CI, Rocha R, Velazquez EJ, PIONEER-HF Investigators. Angiotensin Receptor-Neprilysin Inhibition Based on History of Heart Failure and Use of Renin-Angiotensin System Antagonists. J Am Coll Cardiol. 2020 Sep 1;76(9):1034–1048.
Journal cover image

Published In

J Am Coll Cardiol

DOI

EISSN

1558-3597

Publication Date

September 1, 2020

Volume

76

Issue

9

Start / End Page

1034 / 1048

Location

United States

Related Subject Headings

  • Valsartan
  • Tetrazoles
  • Renin-Angiotensin System
  • Receptors, Angiotensin
  • Prospective Studies
  • Neprilysin
  • Middle Aged
  • Male
  • Humans
  • Heart Failure