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

https://doi.org/10.1016/j.jacc.2016.09.931Get rights and content
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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.)

Key Words

biomarker
chronic heart failure
natriuretic peptide
reduced ejection fraction

Abbreviations and Acronyms

ACE
angiotensin-converting enzyme
ARB
angiotensin receptor blocker
BNP
B-type natriuretic peptide
CHF
congestive heart failure
CI
confidence interval
HF
heart failure
HFrEF
heart failure with reduced ejection fraction
HR
hazard ratio
IQR
interquartile range
NP
natriuretic peptide
NT-proBNP
N-terminal pro–B-type natriuretic peptide
PARADIGM-HF
Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure

Cited by (0)

This study was funded by Novartis. All authors have consulted for and received research support from Novartis, sponsor of the PARADIGM-HF trial. Drs. Prescott, Gong, and Shi are employees of Novartis. Professor McMurray’s employer, University of Glasgow, was paid by Novartis for Professor McMurray’s time spent as co-chairman of the PARADIGM-HF trial. Dr. Packer has served as a consultant for Admittance Technologies, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BioControl, CardioKinetix, CardioMEMS, Cardiorentis, Celyad, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Janssen, Pfizer, Sanofi, Takeda, and ZS Pharma. Dr. Swedberg has received honoraria from Novartis for sponsored lectures; has served as a consultant for AstraZeneca and Amgen and he has also received research support from Servier. Dr. Desai has served as a consultant for St. Jude Medical, Relypsa, Sanofi, and Merck.

Listen to this manuscript's audio summary by JACC Editor-in-Chief Dr. Valentin Fuster.