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Current Hypertension Reports

, Volume 5, Issue 4, pp 346–352 | Cite as

Recent clinical trials with omapatrilat: New developments

  • Anne Zanchi
  • Marc Maillard
  • Michel Burnier
Article

Abstract

Omapatrilat belongs to the vasopeptidase inhibitors, ie, drugs that possess the ability to inhibit simultaneously the membrane-bound zinc metalloproteases, angiotensin-converting enzyme (ACE), and the neutral endopeptidase EC 3.4.24.11 (NEP). Omapatrilat was targeted to treat patients with hypertension and congestive heart failure. The preclinical and early clinical studies conducted with omapatrilat were very promising. Indeed, omapatrilat appeared to be a very potent antihypertensive agent with very favorable effects on cardiac function in heart failure patients. In contrast to these early studies, the large clinical trials were more disappointing. The results of the OCTAVE trial confirmed the antihypertensive efficacy of omapatrilat, but at the price of an angioedema rate more than threefold higher than that of an ACE inhibitor in the overall population (2.17% vs 0.68%), and close to fourfold higher in the black population. In OVERTURE, a large randomized control trial in heart failure, angioedema was also more common with omapatrilat, but the incidence was much lower (0.8% with omapatrilat vs 0.5% with enalapril). However, omapatrilat was not convincingly superior to the ACE inhibitor. Because angioedema is probably a class side effect of vasopeptidase inhibitors, the higher incidence of this potentially life-threatening complication with omapatrilat has likely stopped the development of this new class of agents. The future of vasopeptidase inhibitors will depend on the ability to improve the risk/benefit ratio either by developing agents that produce less angioedema, or by defining more precisely a high-risk population that could take advantage of dual ACE/NEP inhibition.

Keywords

Enalapril Atrial Natriuretic Peptide Lisinopril Angioedema NYHA Functional Class 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Current Science Inc. 2003

Authors and Affiliations

  • Anne Zanchi
  • Marc Maillard
  • Michel Burnier
    • 1
  1. 1.Division of Hypertension and Vascular MedicineLausanneSwitzerland

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