Why is not neprilysin inhibitor used alone? – Discussion
Neprilysin is a neutral endopeptidase involved in the degradation of natriuretic peptides (A, B and C), bradykinin, adrenomedullin, angiotensin II and other vasoactive peptides.
If neprilysin inhibitor is used alone, it will not be effective as angiotensin II levels will rise.
Combining neprilysin inhibitor with angiotensin converting enzyme inhibitor showed superior efficacy, but was associated with serious angioedema.
ARNI (Angiotensin receptor blocker neprilysin inhibitor) valsartan/sacubitril does not inhibit angiotensin converting enzyme inhibitor or aminopeptidase P, was not associated with increased risk of angioedema in the PARADIGM-HF trial .
Omapatrilat, a drug which inhibits all the three enzymes involved in degradation of bradykinin (neprilysin, ACE and aminopeptidase P) was associated with serious angioedema and drug development was discontinued.
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- McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. (Free full text).