Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events - OVERTURE
Study evaluating the use of omapatrilat compared to enalapril in patients with congestive heart failure.
The vasopeptidase inhibitor, omapatrilat, will have improved outcomes when compared to enalapril.
Patients Enrolled: 5770
NYHA Class: Class II (48%), Class III (48%), Class IV (4%)
Mean Follow Up: 14.5 months
Mean Patient Age: Mean 63 years
Mean Ejection Fraction: 24%
1) NYHA Class II-IV congestive heart failure for over 2 months due to ischemic or nonischemic heart disease 2) LVEF <30% 3) Hospitalized for heart failure within the last 12 months 4) Receiving diuretics at the time of enrollment
1) Surgically correctable or reversible cause of heart failure 2) Received or were likely to receive a cardiac transplant or left ventricular assist device 3) Severe primary pulmonary, renal, or hepatic disease 4) History of intolerance to an ACE inhibitor 5) Acute coronary syndrome within the previous month 6) Coronary revascularization or an acute cerebral ischemic event within the previous 3 months 7) Patients with a history of ventricular tachycardia, ventricular fibrillation, or sudden death were not enrolled unless an implantable cardioverter-defibrillator had been placed and had not fired within the previous 2 months. 8) Patients were not allowed to have been hospitalized or to have received any intravenous therapy for heart failure within 48 hours or any intravenous positive inotropic agent within 2 weeks before randomization 9) Systolic blood pressure >180 or <90 mm Hg, a heart rate >130 bpm, serum creatinine >2.5 mg/dL, or serum potassium <3.5 or >5.2 mmol/L.
All cause mortality
Omapatrilat 40 mg orally/day or enalapril 20 mg orally/day
Diuretics, digoxin (60%), beta-blockers (52%), spironolactone (42%)
A trend toward the reduction of the combined endpoint of death or hospitalization for congestive heart failure was found in the omapatrilat group (34% v. 32%;p=0.19[ HR 0.94, 95% CI 0.86-1.03]. There was also a trend toward reduction in the individual event of all cause mortality (18% v. 17%; p=0.34 [RR 0.94; 95% CI 0.83-1.07]).
This trial failed to show that omapatrilat was superior to enalapril in patients with congestive heart failure. The trend was strong enough, however, to show that omapatrilat was not inferior to enalapril and likely is better than placebo. The investigators attribute the lack of benefit seen with omapatrilat to a combination of the factors such as definition of endpoints, inclusion criteria, suboptimal dosing of omapatrilat or simply that omapatrilat was not superior to enalapril. While omapatrilat reduces the morbidity and mortality associated with heart failure it does not provide any benefit beyond the use of enalapril.
Packer M, Califf RM, Konstam MA, et al. Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE). Circulation 2002;106:920-6. Presented by M. Packer at the Annual Meeting of the European Society of Cardiology, September 4, 2002
Keywords: Enalapril, Diuretics, Heart Failure, Thiazepines, Protease Inhibitors, Pyridines
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