title: Combined neutral endopeptidase inhibitors.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: John Radcliffe Hospital, Oxford Heart Centre, Oxford, UK.
authors.forename: Florim
authors.initials: F
authors.lastname: Cuculi
authors.forename: Paul
authors.initials: P
authors.lastname: Erne
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000639:trends; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008954:Models, Biological; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013841:Thiazepines / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D011480:Protease Inhibitors; D011725:Pyridines; D013841:Thiazepines; C106266:omapatrilat; D015260:Neprilysin