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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). This event is less frequent in patients who previously have been treated with an ACE-inhibitor and for this reason this medicine should only be prescribed to patients who have already used an ACE-inhibitor.
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: Sacubitril/valsartan should only be prescribed to heart failure patients who are still symptomatic despite treatment with full dose ACE-inhibitor. It must not be taken by patients currently taking ACE-inhibitors or angiotensin receptor blockers (ARBs).

Also known as:

  • Sacubitril/valsartan
    (Entresto®)

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