Role of BNP vs NT-proBNP Testing in the Age of New Drug Therapies: Sacubitril-Valsartan

Abstract

Sacubitril-valsartan (Entresto), a new dual drug therapy that includes an angiotensin receptor neprilysin (NEP)15 inhibitor (sacubitril), is directed at reducing the risk of cardiovascular death and hospitalization for heart failure (HF) in patients with chronic HF (New York Heart Association classes II–IV) and reduced ejection fraction (HFrEF). Since its approval for the treatment of HFrEF, a commonly raised question has been whether treatment with this drug can complicate the interpretation of B-type natriuretic peptide (BNP) testing results compared to those of the N-terminal proBNP assay because Entresto may interfere with BNP clearance. The clinical and analytical studies addressing this issue are limited. Furthermore, the diversity of both BNP and NT-proBNP assays used in clinical laboratory practice have not been adequately evaluated in clinical trials, and studies to provide an evidence-based conclusion regarding the appropriate assays to use when a patient is on Entresto are lacking. In this article, 5 experts from the US and Europe provide their views regarding this issue. Do you think the differences between BNP and NT-proBNP measurements in patients receiving Entresto are only an early phenomenon because they both seem to be reduced over time? James Januzzi: In the PARADIGM-HF trial, NT-proBNP fell acutely after initiation of Entresto and then continued to drop over time until the end of the trial. Both the enalapril and Entresto arms had a slow, gradual drop in NT-proBNP by the end of trial. This drop likely reflects one of 2 possibilities. First, it may be the subtraction of noncompleters by the end of trial led to a perceived further drop in NT-proBNP (sicker patients that withdrew or died who likely had higher NT-proBNP concentrations). Alternatively, longer treatment with either therapy (angiotensin-converting enzyme inhibitor or angiotensin receptor neprilysin inhibitors) led to further stability, resulting in less synthesis and release of …