Combined drug sacubitril/valsartan -a new era of treatment of chronic heart failure

Abstract

The article describes the possibility of using a new class of angiotensin II/neprilysin receptor inhibitor - sacubitrile/valsartan for the treatment of chronic heart failure (CHF). The role of the natriuretic peptide system in the pathogenesis of CHF and the importance of neurohormonal modulation in modern therapy of patients with heart failure are emphasized. Strategies for introducing exogenous natriuretic peptides and blocking the destruction of natriuretic peptides in the human body are described. The questions of influence on the enzyme neprilysin, which is involved in the metabolism of natriuretic peptides and angiotensin II, are considered. In this regard, the simultaneous inhibition of non-lysine with the suppression of the renin-angiotensin system is promising. The first experience in this direction was the development and study of the drug omapatrilat. The results of multicenter studies of OVERTURE (Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events) and OCTAVE (Omapatrilat Cardiovascular Treatment vs. Enalapril) are presented. An obstacle for the use of omapatrilat in clinical practice was the high frequency of angioedema. To reduce the risk of this complication, a combined drug LCZ696 was designed, consisting of a neprilysin inhibitor - sacubitrile (AHU377) and an angiotensin II receptor blocker (ARB) - valsartan, which, unlike ACE inhibitors, does not inhibit the breakdown of bradykinin. The presence in the composition of LCZ696 of a substance acting on the system of neutral endopeptidases, made this drug the first of a new class of drugs. The results of the PARADIGM-HF study (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial) served as the basis for including the drug sacubitril/valsartan in 2016 in the ACC/AHA/HFSA and ESC guidelines, and later in the Russian recommendations. The article discusses modern approaches to the use of the drug sacubitril/valsartan.