Sacubitril-Valsartan – ABC CARDIOL

ABCHF

Viewpoint

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

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 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.

[…]

Read Full Article

ABC

Original Article

Maximal Oxygen Uptake and Ventilation Improvement Following Sacubitril-Valsartan Therapy

António Valentim Gonçalves et al. Tiago Pereira-da-Silva Ana Galrinho Pedro Rio … Rui Soares Joana Feliciano Rita Ilhão Moreira Sofia Silva Sandra Alves Eunice Capilé Rui Cruz Ferreira

Abstract

Background

Sacubitril/valsartan had its prognosis benefit confirmed in the PARADIGM-HF trial. However, data on cardiopulmonary exercise testing (CPET) changes with sacubitril-valsartan therapy are scarce.

Objective

This study aimed to compare CPET parameters before and after sacubitril-valsartan therapy.

Methods

Prospective evaluation of chronic heart failure (HF) patients with left ventricular ejection fraction ≤40% despite optimized standard of care therapy, who started sacubitril-valsartan therapy, expecting no additional HF treatment. CPET data were gathered in the week before and 6 months after sacubitril-valsartan therapy. Statistical differences with a p-value <0.05 were considered significant.

Results

Out of 42 patients, 35 (83.3%) completed the 6-month follow-up, since 2 (4.8%) patients died and 5 (11.9%) discontinued treatment for adverse events. Mean age was 58.6±11.1 years. New York Heart Association class improved in 26 (74.3%) patients. Maximal oxygen uptake (VO₂max) (14.4 vs. 18.3 ml/kg/min, p<0.001), VE/VCO₂slope (36.7 vs. 31.1, p<0.001), and exercise duration (487.8 vs. 640.3 sec, p<0.001) also improved with sacubitril-valsartan. Benefit was maintained even with the 24/26 mg dose (13.5 vs. 19.2 ml/kg/min, p=0.018) of sacubitril-valsartan, as long as this was the highest tolerated dose.

Conclusions

Sacubitril-valsartan therapy is associated with marked CPET improvement in VO₂max, VE/VCO₂slope, and exercise duration. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)