The nephroprotective effect of sacubitril/valsartan in heart failure: insights from the real-life clinical setting

Sacubitril/valsartan represents the first agent in a new class of drugs developed for heart failure (HF) treatment and termed angiotensin receptor neprilysin (NEP) inhibitors (ARNIs). It is a fixed-dose combination compound containing molecular moieties of valsartan, an angiotensin-type I receptor (AT1)-inhibitor, and the NEP inhibitor sacubitril in a 1:1 molar ratio [1]. Sacubitril is a prodrug that, following oral administration, is rapidly metabolized to the biologically active molecule sacubitrilat. This inhibits the NEP, which is a ubiquitous endopeptidase that is responsible for the breakdown of many vasoactive peptides, including the biologically active natriuretic peptides (NPs), adrenomedullin, substance P, bradykinin, vasoactive intestinal polypeptide, calcitonin gene-related peptide, and enkephalins. Inhibition of NEP increases the levels of these substances, countering the neurohormonal overactivation that contributes to vasoconstriction, sodium retention, and maladaptive...