Benefits and pitfalls of sacubitril/valsartan treatment in patients with hypertension

Abstract

| BENEFICIAL EFFECTS OF SACUBITRIL/VALSATAN IN PATIENTS WITH HYPERTENSIONAlso, a 52-week extension study showed that LCZ696 400 mg either alone or in combination with amlodipine 5 to 10 mg ± hydro-

Angiotensin receptor neprilysin inhibitor as a novel antihypertensive drug: Evidence from Asia and around the globe

“…Neprilysin also degrades amyloid β peptides, the accumulation of which may predispose to Alzheimer disease, age-related macular degeneration, and cerebral amyloid angiopathy. 5,7 This is thus the most concerning issue regarding long-term use of sacubitril/valsartan, which necessitates further research and validation.…”

“…It is a first‐in‐class angiotensin receptor neprilysin inhibitor (ARNi) that is comprised of sacubitril and valsartan in equal moieties. Sacubitril inhibits the actions of neprilysin, a metallopeptidase that degrades multiple biologically active peptides 1,5,7 . Most importantly, neprilysin hydrolyzes natriuretic peptides (NPs), namely atrial natriuretic peptide (ANP), B‐type natriuretic peptide (BNP), and C‐type natriuretic peptide (CNP).…”

“…Sacubitril inhibits the actions of neprilysin, a metallopeptidase that degrades multiple biologically active peptides. 1,5,7 Most importantly, neprilysin hydrolyzes natriuretic peptides (NPs), namely atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). NPs exert diuretic, natriuretic, vasodilatory, and sympatholytic effects, which are thus enhanced by sacubitril and, in the long run, translate into anti-inflammatory, antifibrotic, and antihypertrophic results.…”

“…7,24 Isolated antagonism of neprilysin may thus induce counter-regulatory responses that negates the desirable actions of NPs. Simultaneous suppression of both the RAAS by valsartan and neprilysin by sacubitril exhib-Peptide hormones catabolized by neprilysin and their effects on blood pressures…”

Antisense regulation of atrial natriuretic peptide expression

“…However, more targeted strategies for natriuretic peptide enhancement are desirable, to reduce the risk of adverse effects resulting from accumulation of the several other peptide targets of neprilysin, and to increase therapeutic efficacy. For example, the accumulation of bradykinin may increase risk of angioedema, while accumulation of amyloid β may at least in theory predispose to brain amyloid deposits, and the complex range of vasoactive hormones may predispose to both increased and decreased BP, depending on the patient (4). Therefore, the identification of pathways or molecules that regulate natriuretic peptide expression in CMs is of potential importance.…”