How it works

Entresto is a medication that combines sacubitril and valsartan. It has the potential to be used to treat heart failure.

Once absorbed, sacubitril is converted into its active form, sacubitrilat (LBQ657). This inhibits the effects of neprilysin, an enzyme that naturally cleaves peptides like ANP, BNP, and CNP that are released when the heart is stressed. Sacubitril increases the concentration of these peptides by inhibiting neprilysin, resulting in vasodilation (blood vessel dilation), natriuresis (an increase in sodium excretion in the urine), and diuresis (an increase in the production of urine). Sacubitril belongs to the angiotensin receptor neprilysin inhibitor (ARNI) class of drugs.

Valsartan works by preventing angiotensin II from binding to the AT1 receptor in blood vessels and other tissues such as the adrenal gland. Angiotensin II is a potent vasoconstrictor (narrows blood vessels) that is also involved in aldosterone synthesis and release (the main steroid hormone produced by the adrenal gland). Valsartan opens the arteries (vasodilates) and lowers blood pressure by inhibiting the actions of angiotensin II. Valsartan is in a class of drugs known as angiotensin II receptor antagonists (also called angiotensin II receptor blockers or ARBs).