Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE).

Journal Article (Clinical Trial;Journal Article)

BACKGROUND: Combined inhibition of the angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) may produce greater benefits in heart failure than ACE inhibition alone. METHODS AND RESULTS: We randomly assigned 5770 patients with New York Heart Association class II to IV heart failure to double-blind treatment with either the ACE inhibitor enalapril (10 mg BID, n=2884) or to the ACE-NEP inhibitor omapatrilat (40 mg once daily, n=2886) for a mean of 14.5 months. The primary end point-the combined risk of death or hospitalization for heart failure requiring intravenous treatment--was used prospectively to test both a superiority and noninferiority hypothesis (based on the effect of enalapril in the Studies of Left Ventricular Dysfunction [SOLVD] Treatment Trial). A primary end point was achieved in 973 patients in the enalapril group and in 914 patients in the omapatrilat group (hazard ratio 0.94; 95% CI: 0.86 to 1.03, P=0.187)--a result that fulfilled prespecified criteria for noninferiority but not for superiority. The omapatrilat group also had a 9% lower risk of cardiovascular death or hospitalization (P=0.024) and a 6% lower risk of death (P=0.339). Post hoc analysis of the primary end point with the definition used in the SOLVD Treatment Trial (which included all hospitalizations for heart failure) showed an 11% lower risk in patients treated with omapatrilat (nominal P=0.012). CONCLUSION: Omapatrilat reduces the risk of death and hospitalization in chronic heart failure but was not more effective than ACE inhibition alone in reducing the risk of a primary clinical event. Between-group differences in favor of omapatrilat observed in secondary and post hoc analyses warrant further study.

Full Text

Duke Authors

Cited Authors

  • Packer, M; Califf, RM; Konstam, MA; Krum, H; McMurray, JJ; Rouleau, J-L; Swedberg, K

Published Date

  • August 20, 2002

Published In

Volume / Issue

  • 106 / 8

Start / End Page

  • 920 - 926

PubMed ID

  • 12186794

Electronic International Standard Serial Number (EISSN)

  • 1524-4539

Digital Object Identifier (DOI)

  • 10.1161/01.cir.0000029801.86489.50


  • eng

Conference Location

  • United States