Omapatrilat was noninferior, but not superior, to enalapril for the combined risk of death or heart failure hospitalization (HR 0.94; 95% CI 0.86-1.03; P=0.187).
RCT (n=5,770)
Double-blind
Does omapatrilat reduce the combined risk of death or hospitalization for heart failure requiring intravenous treatment compared to enalapril in patients with NYHA class II to IV chronic heart failure?
Omapatrilat is noninferior, but not superior, to enalapril in reducing the combined risk of death or heart failure hospitalization requiring IV treatment in patients with chronic heart failure.
Effect estimate: HR 0.94 (95% CI 0.86 to 1.03)
Absolute Event Rate: 31.7% vs 33.7%
p-value: p=0.187
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.
Packer et al. (Tue,) conducted a rct in Chronic Heart Failure (n=5,770). Omapatrilat vs. Enalapril (10 mg BID) was evaluated on Combined risk of death or hospitalization for heart failure requiring intravenous treatment (HR 0.94, 95% CI 0.86 to 1.03, p=0.187). Omapatrilat was noninferior, but not superior, to enalapril for the combined risk of death or heart failure hospitalization (HR 0.94; 95% CI 0.86-1.03; P=0.187).