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# Angiotensin receptor-neprilysin inhibitors (ARNI)

A combination that blocks the AT1 receptor and the enzyme neprilysin, so natriuretic peptides last longer. Used in heart failure.

Updated 2026-11-01

## What they are

A class made of one combination so far, sacubitril with valsartan. It treats chronic heart failure, with the clearest benefit when the ejection fraction is reduced, and replaces an ACE inhibitor or ARB in eligible patients.

## Mechanism of action

Neprilysin breaks down natriuretic peptides (ANP, BNP), bradykinin and angiotensin II. Inhibiting it keeps natriuretic peptides active, which promote sodium excretion and vasodilation. Because neprilysin inhibition alone would also raise angiotensin II, it is always paired with an AT1 receptor blocker.

Target: Neprilysin (neutral endopeptidase) and the AT1 receptor

## Key points

- Never given with an ACE inhibitor: at least 36 hours must pass when switching either way, because of angioedema.
- BNP is a neprilysin substrate and rises on treatment; NT-proBNP is not, so it is the marker followed.
- Main adverse effects: hypotension, hyperkalaemia, rise in creatinine and angioedema.
- Contraindicated in pregnancy, like every drug acting on the renin-angiotensin system.

## Drugs in this class

- [**Sacubitril/valsartan** A heart failure combination of a neprilysin inhibitor and an ARB. It reduces cardiovascular deaths and hospital stays… Neprilysin (neutral endopeptidase)](https://durgical.com/en/pharmacology/sacubitril-valsartan/)

## Test yourself

Think of the answer, then tap the question to see it.

## Why is sacubitril always combined with an ARB rather than given alone?

Neprilysin also degrades angiotensin II; inhibiting it alone would raise angiotensin II, so the AT1 receptor is blocked at the same time.

## Why is an ARNI never combined with an ACE inhibitor?

Both raise bradykinin, so together they greatly increase the risk of angioedema.

## Which natriuretic peptide marker is reliable during ARNI treatment?

NT-proBNP, because it is not broken down by neprilysin; BNP itself rises with the drug.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - SACUBITRIL AND VALSARTAN tablet, film coated](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ccfa182e-8a23-42e1-9062-be2655c96208) (DailyMed (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=C09DX04) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 33 (McGraw Hill, 2023).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/angiotensin-receptor-neprilysin-inhibitors/