Context

ACE inhibitors prolong survival in patients with heart failure with reduced ejection fraction (HFrEF) and have served as the backbone of heart failure management for over two decades.1

Natriuretic peptides (NPs) are hormones responsible for maintaining sodium and fluid homoeostasis; their release is triggered by increased myocardial filling pressures. NP benefits include direct vasodilation, increased glomerular filtration rate and reduced release of renin from the kidneys, in addition to natriuresis and diuresis.2 NPs are broken down by the neutral endopeptidase neprilysin, which also helps break down angiotensin II.

In heart failure NP levels are elevated due to hypervolemia but are ineffective at relieving excess volume. One method of increasing NP concentrations is to reduce their degradation …