Cardiovascular
Sacubitril/valsartan
An angiotensin receptor–neprilysin inhibitor (ARNI) — A combination heart-failure drug that improves outcomes beyond an ACE inhibitor or ARB alone.
Education and reference only. This is a plain-language class overview — it deliberately contains no doses. Always check the current Summary of Product Characteristics (SmPC), the BNF and your local formulary before prescribing or administering any medicine.
What it is
Sacubitril/valsartan is a two-in-one tablet for chronic heart failure with a reduced ejection fraction, used in place of an ACE inhibitor or ARB to improve symptoms and survival. It is started and titrated under specialist or structured guidance.
How it works
The valsartan component blocks the angiotensin pathway, like other ARBs. The sacubitril component blocks neprilysin, an enzyme that breaks down beneficial natriuretic peptides — hormones that help the body shed salt and water and relax blood vessels. Together they unload the failing heart more effectively than blocking the angiotensin system alone.
In practice
In practice sacubitril/valsartan has become a cornerstone of treatment for heart failure with reduced ejection fraction, where it reduces hospitalisation and death compared with an ACE inhibitor alone. The single most important safety rule is that it must NOT be combined with an ACE inhibitor: doing so sharply raises the risk of angioedema, so a washout gap of at least 36 hours is left when switching from one. Because it contains an ARB component it carries the familiar cautions — it can raise potassium and affect kidney function, and it lowers blood pressure, so renal function, potassium and blood pressure are checked after starting and up-titrating. It is started at a reduced dose and increased gradually as tolerated, and it is avoided in pregnancy and in anyone with a history of ACE-inhibitor- or ARB-related angioedema.
Examples
Practical use
How to take it & use it well
- Take sacubitril/valsartan twice a day as prescribed, with or without food, at roughly the same times each day.
- Never take it together with an ACE inhibitor such as ramipril or lisinopril, as combining them greatly raises the risk of dangerous swelling (angioedema).
- If switching from an ACE inhibitor, leave the full gap your team advises (around a day and a half) before your first dose to allow a washout.
- Attend blood tests to check your kidney function and potassium, as these are monitored when starting and after dose changes.
- Stand up slowly, especially at first, as the medicine can lower blood pressure and cause dizziness.
- Seek urgent help if you notice swelling of the face, lips, tongue or throat, or difficulty breathing.
Common uses
- Chronic heart failure with reduced ejection fraction
- As a replacement for an ACE inhibitor or ARB in eligible patients
Monitoring
- Renal function, potassium and blood pressure after starting and each up-titration
- Symptoms and tolerability during gradual dose increase
- For any swelling of the face, lips or tongue
Weighing it up
Advantages & disadvantages
Advantages
- Can reduce the risk of hospital admission and death in certain types of heart failure better than an ACE inhibitor alone.
- Helps the heart work more efficiently and can ease breathlessness and fluid build-up over time.
- Combines two actions in a single twice-daily tablet, simplifying treatment.
- An important option for people with reduced heart pumping function who remain symptomatic on standard treatment.
Disadvantages
- Must never be combined with an ACE inhibitor because of the serious risk of angioedema.
- Can lower blood pressure, sometimes causing dizziness, particularly when starting or increasing the dose.
- May raise blood potassium and affect kidney function, so regular blood tests are needed.
- Is not suitable in pregnancy and must be stopped if pregnancy is planned or occurs, as it can harm the baby.
Key safety principles
What to watch for
- NEVER combine with an ACE inhibitor — risk of angioedema; leave at least a 36-hour gap when switching.
- Can raise potassium, reduce kidney function and lower blood pressure (it contains an ARB).
- Avoid in pregnancy and in anyone with previous ACE-inhibitor/ARB angioedema.
Key interactions
What to avoid or check alongside
- Taking it with an ACE inhibitor markedly increases the risk of angioedema, so the two must never be used together and a washout gap is required when switching.
- Combining it with potassium-sparing diuretics such as spironolactone or with potassium supplements can push potassium too high.
- Non-steroidal anti-inflammatory painkillers can reduce its benefit and add to kidney strain, especially in older or dehydrated people.
- Other blood-pressure-lowering medicines can add to the risk of dizziness and low blood pressure.
- Combining it with the diabetes medicine aliskiren is avoided, particularly in people with diabetes or kidney problems.
Patient & carer advice
- Do not take it with an older "-pril" (ACE inhibitor) tablet — there must be a gap when switching
- Report swelling of the face, lips or tongue, or marked dizziness
- Attend your blood tests as the dose is built up
Use with
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Dose and risk decisions for this class often depend on renal function, weight or bleeding/stroke risk. These tools help:
Answers
Sacubitril/valsartan: frequently asked questions
Why can I not take sacubitril/valsartan with an ACE inhibitor?
Using both together sharply raises the risk of angioedema, a dangerous swelling of the face, lips, tongue or throat. The two must never be combined, and a washout gap is needed when switching from one to the other.
What is the washout period when switching from an ACE inhibitor?
You must leave a gap, usually around a day and a half (about 36 hours), between your last ACE inhibitor dose and your first sacubitril/valsartan dose. This lowers the risk of angioedema.
What monitoring do I need on this medicine?
Your team checks your blood pressure, kidney function and potassium level when you start and after dose changes, because the medicine can lower blood pressure and affect the kidneys and potassium.
What should I do if my face or throat swells?
Stop the medicine and seek urgent medical help straight away if your face, lips, tongue or throat swell or you have trouble breathing, as this can be angioedema and is a medical emergency.
Authoritative sources
Always verify against the source
This overview is for orientation. For doses, interactions, contra-indications and the full monograph, use:
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