title: Role of neprilysin inhibitor combinations in hypertension: insights from hypertension and heart failure trials.
abstract: Neprilysin is a neutral endopeptidase and its inhibition increases bioavailability of natriuretic peptides, bradykinin, and substance P, resulting in natriuretic, vasodilatatory, and anti-proliferative effects. In concert, these effects are prone to produce a powerful ventricular unloading and antihypertensive response. LCZ696 (Valsartan/sacubitril) is a first-in-class angiotensin II-receptor neprilysin inhibitor. LCZ696 is a novel drug not only for the treatment of heart failure but it is also likely to be a useful antihypertensive drug and may have a preferential effect on systolic pressure. This review discusses (i) the mechanism of action, pharmacokinetics, and pharmacodynamics of this novel drug, (ii) the efficacy, safety, and tolerability of LCZ696 in treatment of hypertension from the available trials, (iii) evidence from other contemporary trials on combined Neprilysin inhibitors, (iv) future trials and areas of research to identify hypertensive patient populations that would most benefit from LCZ696.
authors.affiliation: Mount Sinai St Luke's & Roosevelt Hospitals, New York, NY, USA.
authors.forename: Chirag
authors.initials: C
authors.lastname: Bavishi
authors.affiliation: Division of Cardiology, Mount Sinai Medical Center, Icahn School of Medicine, 1 Gustave L. Levy Pl, New York, NY 10029, USA Department of Cardiology, Bern University Hospital, Bern, Switzerland messerli.f@gmail.com.
authors.forename: Franz H
authors.initials: FH
authors.lastname: Messerli
authors.affiliation: Mount Sinai St Luke's & Roosevelt Hospitals, New York, NY, USA.
authors.forename: Bernard
authors.initials: B
authors.lastname: Kadosh
authors.affiliation: Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Ruilope
authors.affiliation: Jichi Medical University School of Medicine, Tochigi, Japan.
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Kario
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D045265:Natriuretic Peptides / Q000502:physiology; D015260:Neprilysin / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D045265:Natriuretic Peptides; D015260:Neprilysin
keywords: Angiotensin receptor-neprilysin inhibitor; Hypertension; LCZ696