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Entresto (sacubitril/valsartan)
Introduction vascular resistance and increased
Catherine Russell1 Heart failure has a high prevalence and sodium and water retention. The
MRCP(UK), ST3 Endocrinology and Diabetes poor prognosis, with ~900000 patients RAAS as a target for treatment in
in the UK and 3040% of patients likely heart failure is well established
Miles Fisher1
MD, FRCP, Consultant Physician
to die within one year of diagnosis.1 It is with good evidence for therapeutic
caused by any structural or functional benefit from ACE inhibitors (ACEIs)
Gerry McKay1 abnormality that impairs the ability of and angiotensin II receptor blockers
BSc(Hons) FRCP, Consultant Physician the heart to pump effectively, most (A2RBs). Raised cardiac filling
commonly due to ischaemic heart pressures also cause increased
1
Glasgow Royal Infirmary, Glasgow, UK disease, but can also be as a result of mechanical stretch activating the
valvular, pericardial, endocardial or secretion of precursor natriuretic
conduction problems. One-third of peptides, which in their active form
Correspondence to: patients with heart failure have dia cause vasodilatation, natriuresis and
Dr Catherine Russell, Specialty Trainee, Department of
betes, where a combination of abnor- inhibit the RAAS. The natriuretic
Clinical Pharmacology, Diabetes and Endocrinology,
Glasgow Royal Infirmary, 84 Castle Street, Glasgow
mal systolic function and diastolic peptides that are significant in heart
G40SF, UK; email: Catherine.russell11@nhs.net filling abnormalities contribute to the failure are atrial natriuretic peptide
disorder. Entresto (a combination of (ANP), B natriuretic peptide (BNP)
sacubitril/valsartan) has demonstrated and C natriuretic peptide (CNP). In
efficacy in reducing morbidity and chronic heart failure (CHF), levels of
mortality in patients with heart failure. natriuretic peptide are reduced in
part due to the increased activity of
Pathophysiology neprilysin which enhances the rate of
Elevated cardiac filling pressures, their degradation.
decreased cardiac output and Previous attempts at increasing
reduced oxygen delivery cause an active BNP using the synthetic BNP
activation of the renin angiotensin nesiritide were unsuccessful due to
aldosterone system (RAAS) and sym- associated significant hypotension,
pathetic nervous systems leading over high cost, need for intravenous admin-
time to complications such as myocar- istration route and studies not showing
dial remodelling, increased systemic a reduction in death or hospitalisation
X Neprilysin X
Inactive NPs AT1 receptor AT2 receptor
Vasoconstriction Vasodilation
Blood pressure Blood pressure
Aldosterone (H2O and Natriuresis
Na+ retention) Cardiac remodelling
Cardiac remodelling
Figure 1. Entresto works by a dual effect on the natriuretic system and the renin angiotensin aldosterone system
178 PRACTICAL DIABETES VOL. 33 NO. 5 COPYRIGHT 2016 JOHN WILEY & SONS
Drug notes
Entresto (sacubitril/valsartan)
PRACTICAL DIABETES VOL. 33 NO. 5 COPYRIGHT 2016 JOHN WILEY & SONS 179