ABC Heart Fail Cardiomyop 2022; 2(2): 192-194

Is There Room for Sacubitril-Valsartan in the Treatment of Advanced Heart Failure?

Luis E. Rohde

DOI: 10.36660/abchf.20220029

PARADIGM-HF, published in 2014, was a landmark in the modern pharmacological treatment of heart failure (HF). After several years and numerous clinical trials with disappointing results,^– a new class of drugs was able to produce concrete results in clinically relevant outcomes. In this pivotal study, sacubitril-valsartan, a molecule consisting of a neprilysin inhibitor and an angiotensin-receptor blocker (ARB), drastically reduced hospitalizations for HF, cardiovascular mortality, and overall mortality. The study included more than 8,000 outpatients, mostly New York Heart Association (NYHA) class II or III. Because of its differential mechanism, aimed at amplifying the natriuretic response and the effect of other vasoactive molecules, sacubitril-valsartan could induce pronounced vasodilation, natriuresis and inhibition of cystic fibrosis. These clinical benefits could potentially be extended to the whole spectrum of HF, including more advanced stages of the disease.

Although national and international guidelines have recommended the use of sacubitril-valsartan for HF patients with reduced ejection fraction (HFrEF) and NYHA class ≥II, it is worth mentioning that <1% of patients had NYHA class IV symptoms at randomization in PRADIGM-HF. In addition, only patients who had received and tolerated a single-blind treatment with a stable dose of ARB or angiotensin-converting-enzyme (ACE) inhibitor (run-in periods) and had a systolic blood pressure > 100 mmHg at screening were enrolled. Nearly 20% of patients screened for the trial did not complete the two run-in periods for presenting, among others, low blood pressure and low glomerular filtration rate, both characteristics of advanced HF. Similarly, the PIONEER-HF trial, that tested sacubitril-valsartan in patients with acute congestive HF, also included few patients with NYHA class IV.

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