Effect of angiotensin-converting enzyme or vasopeptidase inhibition on ventricular size and function in patients with heart failure: The Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE) echocardiographic study

Background: Angiotensin-converting enzyme (ACE) inhibition attenuates ventricular remodeling and improves ventricular function in heart failure patients. Vasopeptidase inhibition has shown similar effects in experimental models. Objectives: The OVERTURE echocardiographic study was designed to test the hypothesis that the vasopeptidase inhibitor omapatrilat would attenuate ventricular remodeling and improve ventricular function to a greater extent than an ACE inhibitor. Methods: Three hundred twenty-one patients with heart failure (New York Heart Association class ≥2) were included in the OVERTURE echocardiographic substudy and were randomized to receive enalapril (10 mg twice a day) or omapatrilat (40 mg every day). Echocardiograms were performed at baseline and at 1 year (n = 214). Left ventricular size was estimated by summation of ventricular areas in apical and short-axis views and by calculation of ventricular volumes. Ejection fraction was calculated from ventricular volumes. Results: Combined diastolic and systolic areas and volumes decreased significantly (mean diastolic area change -8.36 cm², 95% CI -9.4 to -7.3 cm²; mean systolic change -8.4 cm², 95% CI -9.5 to -7.3 cm²), and ejection fractions increased significantly (3.6%, 95% CI 2.6% to 4.6%) in both treatment groups from baseline to 1 year. There were no differences in the magnitude of improvement in ventricular size or function based on treatment assignment. Patients who died or were hospitalized for heart failure subsequent to the final assessment demonstrated the least degree of reverse remodeling. Conclusion: Ventricular size and function improved similarly after 1 year with ACE or vasopeptidase inhibition in patients with heart failure. Reverse remodeling was associated with improved outcome.