Comparison of omapatrilat and enalapril in patients with chronic heart failure: The omapatrilat versus enalapril randomized trial of utility in reducing events (OVERTURE)

Milton Packer, Robert M. Califf, Marvin A. Konstam, Henry Krum, John J. McMurray, Jean Lucien Rouleau, Karl Swedberg

Research output: Contribution to journalArticle

496 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)920-926
Number of pages7
JournalCirculation
Volume106
Issue number8
DOIs
StatePublished - Aug 20 2002

Fingerprint

Enalapril
Heart Failure
Peptidyl-Dipeptidase A
Hospitalization
Neprilysin
Left Ventricular Dysfunction
Therapeutics
Protease Inhibitors
Angiotensin-Converting Enzyme Inhibitors
omapatrilat

Keywords

  • Angiotensin-converting enzyme inhibitors
  • Heart failure
  • Omapatrilat

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Comparison of omapatrilat and enalapril in patients with chronic heart failure : The omapatrilat versus enalapril randomized trial of utility in reducing events (OVERTURE). / Packer, Milton; Califf, Robert M.; Konstam, Marvin A.; Krum, Henry; McMurray, John J.; Rouleau, Jean Lucien; Swedberg, Karl.

In: Circulation, Vol. 106, No. 8, 20.08.2002, p. 920-926.

Research output: Contribution to journalArticle

Packer, Milton ; Califf, Robert M. ; Konstam, Marvin A. ; Krum, Henry ; McMurray, John J. ; Rouleau, Jean Lucien ; Swedberg, Karl. / Comparison of omapatrilat and enalapril in patients with chronic heart failure : The omapatrilat versus enalapril randomized trial of utility in reducing events (OVERTURE). In: Circulation. 2002 ; Vol. 106, No. 8. pp. 920-926.
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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.",
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AU - Packer, Milton

AU - Califf, Robert M.

AU - Konstam, Marvin A.

AU - Krum, Henry

AU - McMurray, John J.

AU - Rouleau, Jean Lucien

AU - Swedberg, Karl

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N2 - 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.

AB - 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.

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