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. Burnett, Seethalakshmi Iyer, James L. Januzzi

Research output: Contribution to journalArticlepeer-review

41 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


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