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Monitoring Biomarkers in Patients Receiving Neprilysin Inhibitors


Purpose of Review

To understand the role of neprilysin inhibition in the management of chronic heart failure with reduced ejection fraction (HFrEF) and review effects of neprilysin inhibition on concentrations of natriuretic peptides and other biomarkers.

Recent Findings

Neprilysin inhibition improves cardiovascular outcomes in patients with chronic HFrEF. As bioactive natriuretic peptides are degraded by neprilysin, treatment with sacubitril/valsartan results in an increase in concentrations of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). In contrast, neprilysin inhibition led to reduction in concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Reduction in NT-proBNP to ≤ 1000 pg/mL with neprilysin inhibition improved cardiovascular outcomes in a recent analysis. Other biomarkers may be affected by neprilysin inhibition.


Neprilysin inhibition results in an increase in ANP, BNP, and CNP with corresponding reduction in NT-proBNP concentrations. Other biomarkers may be similarly affected. Given widespread clinical measurement, more data are needed to better understand potential impact on neprilysin inhibition on ability to interpret BNP.

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Funding Sources

Dr. Ibrahim is supported in part by the Dennis and Marilyn Barry Fellowship in Cardiology. Dr. Januzzi is supported in part by the Hutter Family Professorship in Cardiology.

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Correspondence to James L. Januzzi Jr.

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Conflict of Interest

Dr. Januzzi has received grant support from Siemens, Singulex and Prevencio, consulting income from Roche Diagnostics, Critical Diagnostics, Philips, and Novartis, and participates in clinical endpoint committees/data safety monitoring boards for Amgen, Janssen, Abbvie, Pfizer, and Boehringer Ingelheim. Dr. Ibrahim has nothing to disclose.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Heart Failure

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Ibrahim, N.E., Januzzi, J.L. Monitoring Biomarkers in Patients Receiving Neprilysin Inhibitors. Curr Emerg Hosp Med Rep 6, 8–16 (2018).

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  • Biomarker
  • Natriuretic peptide
  • Neprilysin inhibition
  • Heart failure