Neprilysin inhibitors

Neprilysin inhibitors cause an increase in levels of natriuretic peptides which are important in maintaining fluid and sodium balance through natriuresis, diuresis and vasodilation. This reduces blood pressure and assists the treatment of heart failure.

Neprilysin inhibitors such as sacubitril are only used in combination with other medications when used for the treatment of heart failure.

• Neprilysin inhibitor monotherapy for the treatment of heart failure was proven to be unsuccessful possibly because the inhibition of angiotensin II breakdown antagonised the beneficial effects on natriuretic peptides.
• Neprilysin inhibitor and angiotensin-converting enzyme (ACE) inhibitor combination therapy was unsuccessful because of the increased risk of angioedema from dual inhibition of the breakdown of bradykinin.
• Neprilysin inhibitor and angiotensin receptor blocker (ARB) combination therapy was proven to be more beneficial because only one of the enzymes responsible for breakdown of bradykinin is inhibited.

The first neprilysin inhibitor and angiotensin receptor blocker combination was approved under the brand name Entresto (sacubitril and valsartan) in 2015. The addition of sacubitril to valsartan works to produce greater vasodilation and natriuresis.

Entresto is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. It is also indicated for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older.

See Angiotensin receptor blockers and neprilysin inhibitors