sacubitril and valsartan
Entresto combines sacubitril, a neprilysin inhibitor, with valsartan, an angiotensin II receptor blocker. From Novartis, it reduces the risk of cardiovascular death and heart failure hospitalization in adults with chronic heart failure and treats symptomatic heart failure in children aged one year and older.
This page is based on FDA prescribing information for sacubitril and valsartan, cross-checked with DailyMed; the mechanism is explained in plain language, and analogies are used only where they stay accurate.
How it works
Explains what the medicine does in the body, not dosing, side effects, or safety.
An analogy
A failing heart is caught between two signals: helpful peptides that tell the kidneys to shed salt and water, and angiotensin II, which tightens vessels and makes the heart work harder. Sacubitril protects the helpful peptides from being chopped up, while valsartan mutes angiotensin II. Together they lighten the heart's load, so it pumps more easily.
In simple terms
Entresto pairs two medicines in one tablet. Sacubitril blocks neprilysin, the enzyme that breaks down natriuretic peptides, the body's natural signals for relaxing blood vessels and removing salt and water. With more of these peptides active, blood vessels relax and fluid load falls. Valsartan blocks angiotensin II, a hormone that narrows vessels and strains the heart. The combination reduces cardiovascular death and heart failure hospitalizations in adults and treats symptomatic heart failure in children.
In depth
Sacubitril and valsartan combine sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker. Inhibition of neprilysin raises levels of natriuretic peptides, promoting natriuresis, diuresis, and vasodilation, while angiotensin II type 1 receptor blockade counteracts vasoconstriction, sodium retention, and maladaptive cardiac remodelling. In chronic heart failure the combination reduces the risk of cardiovascular death and hospitalization for heart failure, with benefits most clearly evident when left ventricular ejection fraction is below normal, and it reduces NT-proBNP in pediatric patients with symptomatic heart failure and systemic left ventricular systolic dysfunction.
See it in motion
A schematic animation of the mechanism — simplified for clarity, not drawn to scale.
Together they lighten the heart
- A failing heart is caught between two signals: helpful peptides that tell the kidneys to shed salt and water, and angiotensin II, which tightens vessels and makes the heart work harder.
- Sacubitril blocks neprilysin, the enzyme that breaks down natriuretic peptides, the body's natural signals for relaxing blood vessels and removing salt and water.
- With more of these peptides active, blood vessels relax and fluid load falls.
- Valsartan blocks angiotensin II, a hormone that narrows vessels and strains the heart.
Target: Neprilysin and the angiotensin II type 1 receptor
Neprilysin breaks down natriuretic peptides that help the heart shed salt, water, and strain; the angiotensin II receptor drives vessel constriction and heart remodelling. The combination lifts one and blocks the other.
Approved uses
Approved uses differ by country and change over time. Always follow your local prescribing information.
Approved uses in United States
FDA- To reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure, with benefits most clearly evident in patients with left ventricular ejection fraction below normal
- For the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older
Official sources
The statements on this page trace back to these records.
- DailyMed: ENTRESTO (sacubitril and valsartan) official US label
U.S. National Library of Medicine, DailyMed
- U.S. Food and Drug Administration: sacubitril and valsartan prescribing information
U.S. Food and Drug Administration
This page explains how the medicine works — it isn’t the patient leaflet. For anything that applies to you, read the leaflet that came with your medicine or ask your pharmacist.
MedUnfold provides educational content and is not medical advice. Always follow your local prescribing information and healthcare professional.