After having changed the treatment of heart failure with reduced ejection fraction: what are the latest evidences with sacubitril valsartan?

Abstract

Sacubitril/valsartan (SV) is a first in class dual action molecule of the neprilysin (NEP) inhibitor prodrug sacubitril (AHU377) and the angiotensin II receptor (Ang-II) type I antagonist valsartan.[1] It is the first angiotensin receptor-neprilysin inhibitor (ARNI) whose pharmacodynamic effects are consistent with a simultaneous stimulation of the natriuretic peptides system (via NEP inhibition) and the blockade of the renin-angiotensin-aldosterone system (valsartan effect) that finally results in systemic vasodilation, increased diuresis and natriuresis, reduction of plasmatic volume and diminution of peripheral vascular resistance.[1],[2] During 2015, SV was approved by the European Medicine Agency for the treatment of symptomatic adults with a chronic heart failure and reduced ejection fraction (HFrEF), and by the United States Food and Drug Administration to reduce the risk of cardiovascular (CV) death and hospitalization for heart failure (HF) in patients with chronic HFrEF (NYHA Class II–IV).[3],[4] Subsequently, the 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure included SV with a class IB recommendation (patients who remain symptomatic despite optimal treatment),[5] and more emphatically, the latest US guidelines, the 2017 ACC/AHA/ HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure recommended that patients in NYHA class II-III who tolerate an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) should be switched to SV in order to reduce morbidity and mortality risks linked to HF.[6]