Angiotensin Receptor-Neprilysin Inhibitor (ARNi) – Sacubitril/Valsartan

Angiotensin Receptor-Neprilysin Inhibitor (ARNi) is a medicine resulting from the combination of two anti-hypertensive drugs (sacubitril and valsartan) that reduce blood pressure.

Recent studies have shown that this drug may improve length of life, more than ACE-inhibitors, drugs commonly used for the treatment of heart failure. ARNi is currently used for the treatment of patients with heart failure with reduced ejection fraction, which means reduced function of the main pumping chamber. Eligible patients should still be symptomatic despite receiving full medical therapy for heart failure or not able to tolerate adequate dose of ACE-inhibitors.

What they do: The two active substances, sacubitril and valsartan, work in different ways. Valsartan blocks the action of a hormone from the kidney called angiotensin II, which can be harmful in patients with heart failure, by blocking the receptors to which angiotensin II normally attaches. This effect stops the hormone’s harmful effects on the heart, and it allows blood vessels to dilate or widen.

Sacubitril blocks the breakdown of natriuretic peptides produced in the body. Natriuretic peptides cause sodium and water to pass into the urine. This effect reduces the work on the heart and reduces blood pressure. The combined effect of the two medicines reduces the strain of the failing heart.

What are the expected benefits? Sacubitril/valsartan has been shown to reduce hospitalizations for heart failure and to improve survival.

Side effects: ARNI treatment is very well tolerated. However, the most serious, but extremely rare, potential side effect of sacubitril/valsartan can be a serious, allergic reaction called angioedema (rapid swelling of deeper skin tissues as well as the tissues around the throat, causing breathing difficulty).

Sacubitril/valsartan should NOT be started until 36 hours after discontinuing an ACE-inhibitor. Sacubitril/valsartan must not be taken in addition to an ACE-inhibitor or an ARB. It must not be taken by patients who have had cough or have suffered an allergic reaction with ACE-inhibitors or by patients who have had angioedema by any cause in the past. The most common side effects with sacubitril/valsartan (which may affect more than 1 in 10 people) are low blood pressure, high blood potassium levels (hyperkalemia) or mild impairment of kidney function.

Top tips: The most recent ESC Guidelines recommend that sacubitril/valsartan be prescribed to heart failure patients who are still symptomatic despite treatment with full dose ACE-inhibitor or ARB. Sacubitril/valsartan may also be considered in symptomatic patients with reduced ejection fraction who have not been previously treated with an ACE inhibitor or ARB. It must not be taken by patients currently taking ACE-inhibitors or angiotensin receptor blockers (ARBs).

Also known as:

  • Sacubitril/valsartan

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ESC Guidelines for Heart Failure

What patients need to know

This guide for patients from the European Society of Cardiology aims to provide an overview of the latest evidence-based recommendations for the diagnosis and treatment of heart failure.

In particular, it should help patients to understand the:

  • main types of heart failure
  • medicines used to treat heart failure
  • devices that may be appropriate
  • importance of rehabilitation
  • management by a multidisciplinary team
  • importance of self-care in managing your own condition

Learn more


A series of 9 simple, captivating animations explaining heart failure and its treatment.

These narrated animations explain how a healthy heart works, what happens to it in heart failure and how various treatments work to improve your health.


In this section you can watch, listen or read interviews with other people with heart failure and their caregivers.


and share your own views and experiences with other patients, families and caregivers. is a European Society of Cardiology website

The website was developed under the direction of the Heart Failure Association of the European Society of Cardiology (ESC). The ESC is a world leader in the discovery and dissemination of best practices in cardiovascular medicine. Our members and decision-makers are healthcare professionals who volunteer their time and expertise to represent professionals in the field of cardiology in Europe and beyond.

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