Prognostic Implications of Changes in N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Heart Failure

Michael R. Zile, Brian L. Claggett, Margaret F. Prescott, John J V McMurray, Milton Packer, Jean L. Rouleau, Karl Swedberg, Akshay S. Desai, Jianjian Gong, Victor C. Shi, Scott D. Solomon

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Background Natriuretic peptides (NP) have prognostic value in heart failure (HF), although the clinical importance of changes in NP from baseline is unclear. Objectives The authors assessed whether a reduction in N-terminal pro–B-type NP (NT-proBNP) was associated with a decrease in HF hospitalization and cardiovascular mortality (primary endpoint) in patients with HF and reduced ejection fraction, whether treatment with sacubitril/valsartan reduced NT-proBNP below specific partition values more than enalapril, and whether the relationship between changes in NT-proBNP and changes in the primary endpoint were dependent on assigned treatment. Methods In PARADIGM-HF (Prospective Comparison of ARNI [Angiotensin Receptor–Neprilysin Inhibitor] with ACEI [Angiotensin-Converting–Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial), baseline NT-proBNP was measured in 2,080 patients; 1,292 had baseline values >1,000 pg/ml and were reassessed at 1 and 8 months. We related change in NT-proBNP to outcomes. Results One month after randomization, 24% of the baseline NT-proBNP levels >1,000 pg/ml had fallen to ≤1,000 pg/ml. Risk of the primary endpoint was 59% lower in patients with a fall in NT-proBNP to ≤1,000 pg/ml than in those without such a fall. In sacubitril/valsartan-treated patients, median NT-proBNP was significantly lower 1 month after randomization than in enalapril-treated patients, and it fell to ≤1,000 pg/ml in 31% versus 17% of patients treated with sacubitril/valsartan and enalapril, respectively. There was no significant interaction between treatment and the relationship between change in NT-proBNP and the subsequent risk of the primary endpoint. Conclusions Patients who attained a significant reduction in NT-proBNP had a lower subsequent rate of cardiovascular death or HF hospitalization independent of the treatment group. Treatment with sacubitril/valsartan was nearly twice as likely as enalapril to reduce NT-proBNP to values ≤1,000 pg/ml. (Prospective Comparison of ARNI [Angiotensin Receptor–Neprilysin Inhibitor] with ACEI [Angiotensin-Converting–Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) [PARADIGM-HF]; NCT01035255.)

Original languageEnglish (US)
Pages (from-to)2425-2436
Number of pages12
JournalJournal of the American College of Cardiology
Volume68
Issue number22
DOIs
StatePublished - Dec 6 2016

Fingerprint

Brain Natriuretic Peptide
Heart Failure
Enalapril
Angiotensins
Natriuretic Peptides
Mortality
Random Allocation
Hospitalization
Morbidity
Therapeutics
LCZ 696

Keywords

  • biomarker
  • chronic heart failure
  • natriuretic peptide
  • reduced ejection fraction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Zile, M. R., Claggett, B. L., Prescott, M. F., McMurray, J. J. V., Packer, M., Rouleau, J. L., ... Solomon, S. D. (2016). Prognostic Implications of Changes in N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Heart Failure. Journal of the American College of Cardiology, 68(22), 2425-2436. https://doi.org/10.1016/j.jacc.2016.09.931

Prognostic Implications of Changes in N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Heart Failure. / Zile, Michael R.; Claggett, Brian L.; Prescott, Margaret F.; McMurray, John J V; Packer, Milton; Rouleau, Jean L.; Swedberg, Karl; Desai, Akshay S.; Gong, Jianjian; Shi, Victor C.; Solomon, Scott D.

In: Journal of the American College of Cardiology, Vol. 68, No. 22, 06.12.2016, p. 2425-2436.

Research output: Contribution to journalArticle

Zile, MR, Claggett, BL, Prescott, MF, McMurray, JJV, Packer, M, Rouleau, JL, Swedberg, K, Desai, AS, Gong, J, Shi, VC & Solomon, SD 2016, 'Prognostic Implications of Changes in N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Heart Failure', Journal of the American College of Cardiology, vol. 68, no. 22, pp. 2425-2436. https://doi.org/10.1016/j.jacc.2016.09.931
Zile, Michael R. ; Claggett, Brian L. ; Prescott, Margaret F. ; McMurray, John J V ; Packer, Milton ; Rouleau, Jean L. ; Swedberg, Karl ; Desai, Akshay S. ; Gong, Jianjian ; Shi, Victor C. ; Solomon, Scott D. / Prognostic Implications of Changes in N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Heart Failure. In: Journal of the American College of Cardiology. 2016 ; Vol. 68, No. 22. pp. 2425-2436.
@article{302658912e7d46308e911e398794b1a9,
title = "Prognostic Implications of Changes in N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Heart Failure",
abstract = "Background Natriuretic peptides (NP) have prognostic value in heart failure (HF), although the clinical importance of changes in NP from baseline is unclear. Objectives The authors assessed whether a reduction in N-terminal pro–B-type NP (NT-proBNP) was associated with a decrease in HF hospitalization and cardiovascular mortality (primary endpoint) in patients with HF and reduced ejection fraction, whether treatment with sacubitril/valsartan reduced NT-proBNP below specific partition values more than enalapril, and whether the relationship between changes in NT-proBNP and changes in the primary endpoint were dependent on assigned treatment. Methods In PARADIGM-HF (Prospective Comparison of ARNI [Angiotensin Receptor–Neprilysin Inhibitor] with ACEI [Angiotensin-Converting–Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial), baseline NT-proBNP was measured in 2,080 patients; 1,292 had baseline values >1,000 pg/ml and were reassessed at 1 and 8 months. We related change in NT-proBNP to outcomes. Results One month after randomization, 24{\%} of the baseline NT-proBNP levels >1,000 pg/ml had fallen to ≤1,000 pg/ml. Risk of the primary endpoint was 59{\%} lower in patients with a fall in NT-proBNP to ≤1,000 pg/ml than in those without such a fall. In sacubitril/valsartan-treated patients, median NT-proBNP was significantly lower 1 month after randomization than in enalapril-treated patients, and it fell to ≤1,000 pg/ml in 31{\%} versus 17{\%} of patients treated with sacubitril/valsartan and enalapril, respectively. There was no significant interaction between treatment and the relationship between change in NT-proBNP and the subsequent risk of the primary endpoint. Conclusions Patients who attained a significant reduction in NT-proBNP had a lower subsequent rate of cardiovascular death or HF hospitalization independent of the treatment group. Treatment with sacubitril/valsartan was nearly twice as likely as enalapril to reduce NT-proBNP to values ≤1,000 pg/ml. (Prospective Comparison of ARNI [Angiotensin Receptor–Neprilysin Inhibitor] with ACEI [Angiotensin-Converting–Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) [PARADIGM-HF]; NCT01035255.)",
keywords = "biomarker, chronic heart failure, natriuretic peptide, reduced ejection fraction",
author = "Zile, {Michael R.} and Claggett, {Brian L.} and Prescott, {Margaret F.} and McMurray, {John J V} and Milton Packer and Rouleau, {Jean L.} and Karl Swedberg and Desai, {Akshay S.} and Jianjian Gong and Shi, {Victor C.} and Solomon, {Scott D.}",
year = "2016",
month = "12",
day = "6",
doi = "10.1016/j.jacc.2016.09.931",
language = "English (US)",
volume = "68",
pages = "2425--2436",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "22",

}

TY - JOUR

T1 - Prognostic Implications of Changes in N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Heart Failure

AU - Zile, Michael R.

AU - Claggett, Brian L.

AU - Prescott, Margaret F.

AU - McMurray, John J V

AU - Packer, Milton

AU - Rouleau, Jean L.

AU - Swedberg, Karl

AU - Desai, Akshay S.

AU - Gong, Jianjian

AU - Shi, Victor C.

AU - Solomon, Scott D.

PY - 2016/12/6

Y1 - 2016/12/6

N2 - Background Natriuretic peptides (NP) have prognostic value in heart failure (HF), although the clinical importance of changes in NP from baseline is unclear. Objectives The authors assessed whether a reduction in N-terminal pro–B-type NP (NT-proBNP) was associated with a decrease in HF hospitalization and cardiovascular mortality (primary endpoint) in patients with HF and reduced ejection fraction, whether treatment with sacubitril/valsartan reduced NT-proBNP below specific partition values more than enalapril, and whether the relationship between changes in NT-proBNP and changes in the primary endpoint were dependent on assigned treatment. Methods In PARADIGM-HF (Prospective Comparison of ARNI [Angiotensin Receptor–Neprilysin Inhibitor] with ACEI [Angiotensin-Converting–Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial), baseline NT-proBNP was measured in 2,080 patients; 1,292 had baseline values >1,000 pg/ml and were reassessed at 1 and 8 months. We related change in NT-proBNP to outcomes. Results One month after randomization, 24% of the baseline NT-proBNP levels >1,000 pg/ml had fallen to ≤1,000 pg/ml. Risk of the primary endpoint was 59% lower in patients with a fall in NT-proBNP to ≤1,000 pg/ml than in those without such a fall. In sacubitril/valsartan-treated patients, median NT-proBNP was significantly lower 1 month after randomization than in enalapril-treated patients, and it fell to ≤1,000 pg/ml in 31% versus 17% of patients treated with sacubitril/valsartan and enalapril, respectively. There was no significant interaction between treatment and the relationship between change in NT-proBNP and the subsequent risk of the primary endpoint. Conclusions Patients who attained a significant reduction in NT-proBNP had a lower subsequent rate of cardiovascular death or HF hospitalization independent of the treatment group. Treatment with sacubitril/valsartan was nearly twice as likely as enalapril to reduce NT-proBNP to values ≤1,000 pg/ml. (Prospective Comparison of ARNI [Angiotensin Receptor–Neprilysin Inhibitor] with ACEI [Angiotensin-Converting–Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) [PARADIGM-HF]; NCT01035255.)

AB - Background Natriuretic peptides (NP) have prognostic value in heart failure (HF), although the clinical importance of changes in NP from baseline is unclear. Objectives The authors assessed whether a reduction in N-terminal pro–B-type NP (NT-proBNP) was associated with a decrease in HF hospitalization and cardiovascular mortality (primary endpoint) in patients with HF and reduced ejection fraction, whether treatment with sacubitril/valsartan reduced NT-proBNP below specific partition values more than enalapril, and whether the relationship between changes in NT-proBNP and changes in the primary endpoint were dependent on assigned treatment. Methods In PARADIGM-HF (Prospective Comparison of ARNI [Angiotensin Receptor–Neprilysin Inhibitor] with ACEI [Angiotensin-Converting–Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial), baseline NT-proBNP was measured in 2,080 patients; 1,292 had baseline values >1,000 pg/ml and were reassessed at 1 and 8 months. We related change in NT-proBNP to outcomes. Results One month after randomization, 24% of the baseline NT-proBNP levels >1,000 pg/ml had fallen to ≤1,000 pg/ml. Risk of the primary endpoint was 59% lower in patients with a fall in NT-proBNP to ≤1,000 pg/ml than in those without such a fall. In sacubitril/valsartan-treated patients, median NT-proBNP was significantly lower 1 month after randomization than in enalapril-treated patients, and it fell to ≤1,000 pg/ml in 31% versus 17% of patients treated with sacubitril/valsartan and enalapril, respectively. There was no significant interaction between treatment and the relationship between change in NT-proBNP and the subsequent risk of the primary endpoint. Conclusions Patients who attained a significant reduction in NT-proBNP had a lower subsequent rate of cardiovascular death or HF hospitalization independent of the treatment group. Treatment with sacubitril/valsartan was nearly twice as likely as enalapril to reduce NT-proBNP to values ≤1,000 pg/ml. (Prospective Comparison of ARNI [Angiotensin Receptor–Neprilysin Inhibitor] with ACEI [Angiotensin-Converting–Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) [PARADIGM-HF]; NCT01035255.)

KW - biomarker

KW - chronic heart failure

KW - natriuretic peptide

KW - reduced ejection fraction

UR - http://www.scopus.com/inward/record.url?scp=84999751857&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84999751857&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2016.09.931

DO - 10.1016/j.jacc.2016.09.931

M3 - Article

C2 - 27908347

AN - SCOPUS:84999751857

VL - 68

SP - 2425

EP - 2436

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 22

ER -