title: Potential Expanded Indications for Neprilysin Inhibitors.
abstract: The goal of this article is to review potential expanded indications for neprilysin inhibitors. This article reviews the rationale and design for ongoing and future trials of sacubitril/valsartan in cardiovascular and non-cardiovascular disease.
  
  
  
  Randomized trial data are lacking for use of sacubitril/valsartan in acute heart failure and advanced heart failure. Mechanistic data from animal studies suggest a role for neprilysin inhibition in the treatment of post-myocardial infarction systolic dysfunction and heart failure with preserved ejection fraction. Beyond the cardiovascular system, renal and neurological function may be impacted by neprilysin inhibition. Forthcoming randomized trials will address the clinical impact of sacubitril/valsartan on these conditions. Neprilysin inhibition with sacubitril/valsartan offers a new therapeutic strategy with a broad range of potential therapeutic actions. In PARADIGM-HF, the combination of neprilysin and RAAS inhibition was proven to be superior to enalapril for patients with stable NYHA class II-III heart failure and reduced left ventricular ejection fraction. Preliminary data suggests it may also have a role in other cardiovascular and non-cardiovascular disease. Several ongoing and planned studies will determine the extent of its benefit for these other indications.
authors.affiliation: Cardiovascular Division, Washington University School of Medicine, 660 S. Euclid Ave., Box 8086, St Louis, MO, 63110, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Riddell
authors.affiliation: Cardiovascular Division, Washington University School of Medicine, 660 S. Euclid Ave., Box 8086, St Louis, MO, 63110, USA. jvader@wustl.edu.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Vader
mesh_terms: D000613:Aminobutyrates / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D001713:Biphenyl Compounds; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D013777:Tetrazoles / Q000627:therapeutic use*; D000068756:Valsartan
chemical_list: D000613:Aminobutyrates; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D004338:Drug Combinations; D013777:Tetrazoles; D000068756:Valsartan; D015260:Neprilysin; C549068:sacubitril and valsartan sodium hydrate drug combination
keywords: Cardiovascular disease; Heart failure; Neprilysin inhibitors; Sacubitril/valsartan