Neprilysin Inhibition in Heart Failure with Reduced Ejection Fraction: A Clinical Review

@article{King2015NeprilysinII,
  title={Neprilysin Inhibition in Heart Failure with Reduced Ejection Fraction: A Clinical Review},
  author={Jordan B. King and Adam P. Bress and Austin D. Reese and Mark A. Munger},
  journal={Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy},
  year={2015},
  volume={35}
}
  • J. KingA. Bress M. Munger
  • Published 1 September 2015
  • Medicine
  • Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
There has been a 10‐year hiatus in the approval of a new pharmacotherapy for patients with chronic heart failure with a reduced ejection fraction (HFrEF). Combining an angiotensin receptor blocker, valsartan, with sacubitril, an inhibitor of neprilysin, results in increasing levels of natriuretic peptides that counterbalance high circulating levels of neurohormones in HFrEF. This has resulted in the development of a new agent, LCZ696. A comprehensive overview of LCZ696, its pharmacology, its… 

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LCZ696, an angiotensin receptor neprilysin inhibitor composed of a nepriolysisin inhibitor prodrug and the angiotENSin receptor antagonist valsartan, has proven effective in hypertension, has shown promise in a pilot trial of heart failure with preserved ejection fraction, and is being tested in a large outcomes trial ofheart failure with reduced ejections fraction.

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The role of neprilysin in the degradation of natriuretic and other vasoactive peptides, including bradykinin and adrenomedullin is described and 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 is discussed.

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