Elsevier

Heart Failure Clinics

Volume 14, Issue 4, October 2018, Pages 479-491
Heart Failure Clinics

Sacubitril/Valsartan: The Newest Neurohormonal Blocker for Guideline-Directed Medical Therapy for Heart Failure

https://doi.org/10.1016/j.hfc.2018.06.012Get rights and content

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Key points

  • The burden of heart failure is projected to increase over the next decade, and it is predicted that 1 in every 33 Americans will be affected by heart failure.

  • The recent addition of the combination of sacubitril/valsartan (LCZ696) to guideline-directed medical therapies should ameliorate this burden.

  • Neprilysin inhibition is associated with significant improvements in survival.

  • Despite substantial reductions in mortality with neprilysin inhibition, the mortality rate among patients with heart

Pharmacology

Sacubitril, a prodrug, is an inhibitor of neprilysin, a neutral endopeptidase, that is responsible for degradation of biologically active vasoactive peptides, including natriuretic peptides (brain natriuretic peptide [BNP] and N-terminal [NT]-proBNP) and bradykinin (Figs. 1 and 2). ProBNPs convert into NT-proBNP and BNP. BNP acts by natriuresis, diuresis, vasodilatation, antiproliferative vascular effects, and decreased sympathetic tone. Degradation of BNP into breakdown products is inhibited

Neurohormonal blockade

The Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF3) showed that more patients in New York Heart Association (NYHA) class 2 and class 3 die of sudden death (Fig. 3). In NYHA class 2, 64% died of sudden death; in NYHA class 3, 59% died of sudden death; in class 2 only 12% died of systolic heart failure; in class 3 only 26% died of pump function or heart failure. In NYHA class 4, 56% died of loss of pump function or heart failure; only 33% died of sudden

Summary

Neprilysin inhibition is associated with significant improvements in survival. Despite substantial reductions in mortality with neprilysin inhibition, the mortality rate among patients with heart failure remains high around 20% over 2 years in the intervention arm of PARADIGM-HF, suggesting that opportunities to reduce mortality in heart failure remain.

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  • Disclosure: The author has nothing to disclose.

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