Sacubitril with valsartan

How it works

Sacubitril is metabolised to a neprilysin inhibitor that increases beneficial natriuretic peptides promoting natriuresis and vasodilatation, while valsartan blocks the angiotensin-II type-1 receptor; the combined effect reduces preload, afterload and harmful neurohormonal activation.

Prescribing in practice

• Never co-administer with an ACE inhibitor and allow a washout of at least 36 hours when switching from one, because concurrent neprilysin and ACE inhibition substantially increases the risk of angioedema.
• Avoid in pregnancy and in patients with a history of ACE-inhibitor- or angiotensin-receptor-blocker-related angioedema, and use with caution in significant renal or hepatic impairment.
• It can cause hypotension, hyperkalaemia and renal impairment, so monitor closely particularly during initiation and up-titration.

Monitoring

Monitor blood pressure, renal function and serum potassium at baseline and after each dose change, with closer review in renal impairment or volume depletion.

Counselling the patient

• Seek urgent help for any swelling of the face, lips, tongue or throat.
• Do not take this with an ACE-inhibitor medicine and observe the gap when switching.
• Report dizziness, which may indicate low blood pressure, and tell your doctor if you become pregnant.

Evidence & guidelines

The PARADIGM-HF trial showed sacubitril-valsartan reduced cardiovascular death and heart-failure hospitalisation compared with enalapril, and it is recommended by NICE for heart failure with reduced ejection fraction.