Effect of Neprilysin Inhibition on Various Natriuretic Peptide Assays

Nasrien E. Ibrahim, Cian P. McCarthy, Shreya Shrestha, Hanna K. Gaggin, Renata Mukai, Jackie Szymonifka, Fred S. Apple, John C Jr. Burnett, Seethalakshmi Iyer, James L. Januzzi

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20 Scopus citations


Background: With sacubitril/valsartan treatment, B-type natriuretic peptide (BNP) concentrations increase; it remains unclear whether change in BNP concentrations is similar across all assays for its measurement. Effects of sacubitril/valsartan on atrial natriuretic peptide (ANP) concentrations in patients are unknown. Lastly, the impact of neprilysin inhibition on mid-regional pro-ANP (MR-proANP), N-terminal pro-BNP (NT-proBNP), proBNP 1-108 , or C-type natriuretic peptide (CNP) is not well understood. Objectives: This study sought to examine the effects of sacubitril/valsartan on results from different natriuretic peptide assays. Methods: Twenty-three consecutive stable patients with heart failure and reduced ejection fraction were initiated and titrated on sacubitril/valsartan. Change in ANP, MR-proANP, BNP (using 5 assays), NT-proBNP (3 assays), proBNP 1-108 , and CNP were measured over 3 visits. Results: Average time to 3 follow-up visits was 22, 46, and 84 days. ANP rapidly and substantially increased with initiation and titration of sacubitril/valsartan, more than doubling by the first follow-up visit (+105.8%). Magnitude of ANP increase was greatest in those with concentrations above the median at baseline (+188%) compared with those with lower baseline concentrations (+44%); ANP increases were sustained. Treatment with sacubitril/valsartan led to inconsistent changes in BNP, which varied across methods assessed. Concentrations of MR-proANP, NT-proBNP, and proBNP 1-108 variably declined after treatment; whereas CNP concentrations showed no consistent change. Conclusions: Initiation and titration of sacubitril/valsartan led to variable changes in concentrations of multiple natriuretic peptides. These results provide important insights into the effects of sacubitril/valsartan treatment on individual patient results, and further suggest the benefit of neprilysin inhibition may be partially mediated by increased ANP concentrations.

Original languageEnglish (US)
Pages (from-to)1273-1284
Number of pages12
JournalJournal of the American College of Cardiology
Issue number11
StatePublished - Mar 26 2019



  • biomarkers
  • heart failure
  • natriuretic peptides
  • neprilysin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Ibrahim, N. E., McCarthy, C. P., Shrestha, S., Gaggin, H. K., Mukai, R., Szymonifka, J., Apple, F. S., Burnett, J. C. J., Iyer, S., & Januzzi, J. L. (2019). Effect of Neprilysin Inhibition on Various Natriuretic Peptide Assays. Journal of the American College of Cardiology, 73(11), 1273-1284. https://doi.org/10.1016/j.jacc.2018.12.063