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. 2019 Mar 26;73(11):1273-1284.
doi: 10.1016/j.jacc.2018.12.063.

Effect of Neprilysin Inhibition on Various Natriuretic Peptide Assays

Nasrien E Ibrahim  1 , Cian P McCarthy  2 , Shreya Shrestha  2 , Hanna K Gaggin  1 , Renata Mukai  2 , Jackie Szymonifka  3 , Fred S Apple  4 , John C Burnett Jr  5 , Seethalakshmi Iyer  5 , James L Januzzi Jr  6
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Free article

Effect of Neprilysin Inhibition on Various Natriuretic Peptide Assays

Nasrien E Ibrahim et al. J Am Coll Cardiol. .
Free article

Abstract

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), proBNP1-108, 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), proBNP1-108, 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 proBNP1-108 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.

Keywords: biomarkers; heart failure; natriuretic peptides; neprilysin.

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