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.


OBJECTIVE
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 > or = 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.


CONCLUSIONS
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.
Solomon
Scott D
SD
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02445, USA. ssolomon@rics.bwh.harvard.edu
Skali
Hicham
H
Bourgoun
Mikhail
M
Fang
James
J
Ghali
Jalal K
JK
Martelet
Michel
M
Wojciechowski
Dariusz
D
Ansmite
Baiba
B
Skards
Janis
J
Laks
Toivo
T
Henry
David
D
Packer
Milton
M
Pfeffer
Marc A
MA
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D015331:Cohort Studies; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D009929:Organ Size / Q000187:drug effects; D016016:Proportional Hazards Models; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D015203:Reproducibility of Results; D013318:Stroke Volume / Q000187:drug effects*; D016019:Survival Analysis; D013841:Thiazepines / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011480:Protease Inhibitors; D011725:Pyridines; D013841:Thiazepines; C106266:omapatrilat; D004656:Enalapril; D009320:Atrial Natriuretic Factor; D015260:Neprilysin