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Related Experiment Videos

Recent clinical trials with omapatrilat: new developments.

Anne Zanchi1, Marc Maillard, Michel Burnier

  • 1Division of Hypertension and Vascular Medicine, Av. P. Decker, CHUV, 1011 Lausanne, Switzerland.

Current Hypertension Reports
|July 8, 2003
PubMed
Summary

Omapatrilat, a dual angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) inhibitor, showed antihypertensive efficacy but a higher angioedema risk. This safety concern likely halted development of this vasopeptidase inhibitor class.

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Area of Science:

  • Pharmacology
  • Cardiovascular Medicine

Background:

  • Omapatrilat is a vasopeptidase inhibitor targeting both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP).
  • Preclinical and early clinical studies suggested promising efficacy for hypertension and heart failure.

Purpose of the Study:

  • To evaluate the efficacy and safety of omapatrilat in large-scale clinical trials for hypertension and heart failure.
  • To assess the risk-benefit profile of dual ACE/NEP inhibition compared to ACE inhibitors alone.

Main Methods:

  • The OCTAVE trial assessed omapatrilat's antihypertensive efficacy and safety.
  • The OVERTURE trial evaluated omapatrilat in heart failure patients compared to enalapril.

Main Results:

  • OCTAVE confirmed omapatrilat's antihypertensive efficacy but revealed a threefold higher angioedema rate versus ACE inhibitors, particularly in Black populations.

Related Experiment Videos

  • OVERTURE showed a slightly higher angioedema incidence with omapatrilat in heart failure, without clear superiority over enalapril.

    • Conclusions:

    • The increased incidence of angioedema, a potentially life-threatening side effect, is a significant safety concern for omapatrilat.
    • Further development of vasopeptidase inhibitors hinges on improving their safety profile or identifying specific patient populations who benefit from dual ACE/NEP inhibition.