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Does neprilysin inhibition improve outcomes in patients with heart failure?
Does neprilysin inhibition improve outcomes in patients with heart failure?
This review outlines the historical development and scientific rationale of neprilysin inhibition, highlighting the landmark success of sacubitril/valsartan in heart failure.
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Supports ARNI use in HFrEF; leaves open refinement of neprilysin-based therapies.
This review describes the role of neprilysin (also known as neutral endopeptidase or enkephalinase) in the degradation of natriuretic and other vasoactive peptides, including bradykinin and adrenomedullin. The initial development of neprilysin inhibitors, then angiotensin converting enzyme-neprilysin inhibitors and, most recently, the angiotensin receptor neprilysin inhibitor (ARNI) LCZ696 (sacubitril valsartan) as an extension of the nurohumoral basis for the treatment of heart failure is also summarised. Finally, the implications of the compelling benefits of LCZ696 compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF) is discussed.
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John J.V. McMurray (2015) studied this question.
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