Published online before print July 29, 2002, doi: 10.1161/01.CIR.0000029801.86489.50
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(Circulation. 2002;106:920.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Comparison of Omapatrilat and Enalapril in Patients With Chronic Heart Failure
The Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE)
From the College of Physicians and Surgeons (M.P.), Columbia University, New York, NY; Duke Clinical Research Institute (R.M.C.), Durham, NC; Monash University (H.K.), Prahran Victoria, Australia; Tufts University School of Medicine (M.A.K.), Boston, Mass; University of Glasgow (J.J.M.), Glasgow, United Kingdom; University Health Network and Mount Sinai Hospital (J.-L.R.), Toronto, Canada; and Sahlgrenska Univerity (K.S.), Göteborg, Sweden.
Correspondence to Dr Milton Packer, Division of Circulatory Physiology, Columbia University, College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032. E-mail mp65{at}Columbia.edu
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.
Key Words: heart failure • angiotensin-converting enzyme inhibitors • omapatrilat
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