Combined neutral endopeptidase inhibitors

Expert Opin Investig Drugs. 2011 Apr;20(4):457-63. doi: 10.1517/13543784.2011.556617. Epub 2011 Feb 15.

Abstract

Introduction: The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathophysiology of hypertension and heart failure. ACE inhibitors, angiotensin receptor II blockers (AT-II blockers) and aldosterone antagonists have been used to tackle the RAAS in the past but combined ACE and neutral endopeptidase (NEP) inhibitors have been shown to be more potent in reducing blood and especially pulse pressure in patients with hypertension.

Areas covered: Different NEP inhibitors have been tested but omapatrilat is the most widely studied in the setting of hypertension, heart failure and chronic angina. We have undertaken a PubMed search on NEP with a special focus on omapatrilat and its efficacy in hypertension and heart failure. The incidence of angioedema is more frequent in patients taking combined ACE and NEP inhibitors and this has prevented these medications from finding a widespread use. Combinations of NEP inhibitors and AT-II blockers are currently being studied and have been shown to reduce the blood pressure significantly. These medications have so far not been associated with angioedema and have a great potential to be safe and effective alternatives in the near future.

Expert opinion: NEP inhibitors were effective in the treatment of hypertension and heart failure but the relatively high incidence of angioedema stopped their widespread use. New hope has risen with the introduction of combined NEP inhibitors and AT-II blockers and early studies are encouraging.

Publication types

  • Review

MeSH terms

  • Angiotensin Receptor Antagonists / administration & dosage
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Drug Therapy, Combination / trends
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Models, Biological
  • Neprilysin / antagonists & inhibitors*
  • Protease Inhibitors / administration & dosage
  • Protease Inhibitors / therapeutic use*
  • Pyridines / administration & dosage
  • Pyridines / therapeutic use*
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology
  • Thiazepines / administration & dosage
  • Thiazepines / therapeutic use*

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Protease Inhibitors
  • Pyridines
  • Thiazepines
  • omapatrilat
  • Neprilysin