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

Abstract

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.

• Authors: Milton Packer, Robert M Califf, Marvin A Konstam, Henry Krum, John J McMurray, Jean-Lucien Rouleau, Karl Swedberg
• Journal: Circulation (Circulation) Vol. 106 Issue 8 Pg. 920-6 (Aug 20 2002) ISSN: 1524-4539 [Electronic] United States
• PMID: 12186794 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Protease Inhibitors
• Pyridines
• Thiazepines
• omapatrilat
• Enalapril
• Neprilysin

Topics

• Angiotensin-Converting Enzyme Inhibitors (adverse effects, therapeutic use)
• Chronic Disease
• Disease-Free Survival
• Double-Blind Method
• Enalapril (adverse effects, therapeutic use)
• Endpoint Determination
• Female
• Heart Failure (drug therapy, mortality)
• Humans
• Male
• Middle Aged
• Neprilysin (antagonists & inhibitors)
• Protease Inhibitors (adverse effects, therapeutic use)
• Pyridines (adverse effects, therapeutic use)
• Thiazepines (adverse effects, therapeutic use)