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UKCPA viewpoint: Entresto

Pharmacists are likely to soon start seeing prescriptions for Entresto – a new treatment for heart failure, says Alison Warren, consultant pharmacist in cardiology.

Heart failure affects 1-2 per cent of the population, with some 25,000 new cases diagnosed a year. With an ageing population, the number of people living with heart failure is predicted to increase by at least 50 per cent over the next 25 years.

The commonest symptoms result from fluid retention and include shortness of breath, general tiredness and muscle weakness. Patients with left ventricular systolic dysfunction (LVSD) have a reduced ability for the heart to pump fluid around the body, resulting in a reduced ejection fraction (EF).

Drug treatment

Diuretics are invaluable in managing the symptoms of fluid overload. The treatments that reduce mortality target neurohormonal pathways that are activated in the failing heart.

Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) in cases of ACEI intolerance and a beta-blocker licensed for the management of heart failure are prescribed and titrated to the maximum tolerated dosages.

A mineralocorticoid receptor antagonist (spironolactone or eplerenone) should also be considered for symptomatic patients. However, despite use of these medicines, mortality remains higher than for many cancers and the search for more effective treatments continues.

New treatment option

Naturetic peptides (NPs) play a significant role in water and salt haemostasis and high levels are found in patents with chronic heart failure. The PARADIGM trial tested whether increasing NP levels by reducing their breakdown with the neprilysin inhibitor (NI) sacubitril would be beneficial.

As inhibition of neprilysin enhances the renin-angiotensin system, co-prescribing with an angiotensin receptor blocker is essential (as it cannot be prescribed with an ACEI due to a very high incidence of angio-oedema).

In the trial (n=8,442) sacubitril plus valsartan led to a 20 per cent relative risk reduction in the combined end-point of death from cardiovascular causes and hospitalisation for heart failure when compared with enalapril. As a result sacubitril plus valsartan (Entresto) is licensed and offers a new treatment option for heart failure patients.

It was approved by NICE in April 2016 for patients:
• With NYHA heart failure class II-IV symptoms and
• With a left ventricular ejection fraction ≤ 35 per cent and
• Who are taking a stable dose of ACE or ARB.

Treatment should be started by a heart failure specialist with access to a multidisciplinary heart failure team with dose titration and monitoring (renal function, potassium and blood pressure) being undertaken.

Key messages

Pharmacists in all settings can play a key role in ensuring:
• The patient is aware of the switching requirements
• The previous ACEI or ARB has been discontinued and monitoring is in place.

A wash-out period of at least 36 hours is needed if switching from an ACEI. For ARBs there is no requirement for a washout period – when the next dose is due this can be replaced with the new medication.

Patients must be aware of the switching requirements

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