Abstract

ROLE OF NEPRILYSIN INHIBITORS COMBINATIONS IN CARDIOVASCULAR DISEASE

Jagdish Kakadiya*, Parth Patel, Kalpit Patel, Umesh Upadhyay

Abstract

Neprilysin is a neutral endopeptidase enzyme that contributes to the breakdown of the biologically active natriuretic peptides and its inhibition increases bioavailability of natriuretic peptides, bradykinin, and substance P, resulting in natriuretic, vasodilatatory, and anti-proliferative effects. Inhibiting neprilysin has been a therapeutic target for several compounds that have been tested in cardiovascular disease, including ecadotril, candoxatril, omapatrilat, and LCZ696 (Valsartan/sacubitril). Although ecadotril, candoxatril, and omapatrilat were initially tested in hypertension and/or heart failure, lack of efficacy and side effects led to discontinuation of their development. LCZ696 is a first-in-class angiotensin receptor Neprilysin inhibitor that has been developed for use in heart failure. In concert, these effects are prone to produce a powerful ventricular unloading and antihypertensive response. Some specific advantage of this drug like a) novel mechanism of action, pharmacokinetics, and pharmacodynamics b) In hypertension available data of trials better efficacy, safety, and tolerability of LCZ696 c) evidence from other contemporary trials on combined Neprilysin inhibitors d) In future trials and areas of research, LCZ696 combination is most benefit in hypertensive patient. In future prospect, Neprilysin inhibitors alone and its combination with other antihypertensive agents use in cardiovascular disease.

Keywords: Natriuretic peptide, Neprilysin, LCZ696 (Valsartan + Sacubitril)