For quite some time, the standard of care for heart failure with reduced ejection fraction (HFrEF) has seen the use of beta-adrenergic blockers, angiotensin-converting enzyme (ACE) inhibitors, and spironolactone.

Learning objectives

After reading this article, pharmacists should be able to:

  • Identify the indications for sacubitril/valsartan and its place in therapy
  • Discuss the pharmacology of sacubitril/valsartan
  • Describe contraindications, precautions and adverse e­ffects related to sacubitril/valsartan.

Competencies (2016) addressed: 1.3, 3.2, 3.3, 3.5.

Angiotensin II receptor antagonists (ARBs) are used for those unable to take ACE inhibitors.1 Maximising such therapy has improved the life of those with HFrEF by improving their level of function, reducing their rate of hospital admissions, and delaying death. A new additional therapy, sacubitril (a neprilysin inhibitor), is now available and seems to o­ffer an alternative to the ACE inhibitor, with perhaps a better outcome for these patients.

So what is this enzyme neprilysin?

We produce natriuretic peptides when there is cardiac wall stretch due to increased volume or pressure.2,3 These peptides improve sodium excretion from the kidneys promoting diuresis. Natriuretic peptides also cause vasodilation,3 which in conjunction with the natriuresis leads to a reduction in pre-load of the ventricles. All are biological actions that are bene‑ cial to patients with HFrEF. Natriuretic peptides are broken down by the endopeptidase, neprilysin; so inhibition of this enzyme promotes biological actions of natriuretic peptides.1–3

Recently, there has been interest in the therapeutic potential of natriuretic peptides in patients with heart failure. It made

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