Outcome of patients with congestive heart failure treated with standard versus high doses of enalapril: a multicenter study. High Enalapril Dose Study Group.
OBJECTIVE
We sought to prospectively and randomly compare survival with clinical and hemodynamic variables in patients with congestive heart failure (CHF) treated with standard versus high doses of enalapril.


BACKGROUND
Angiotensin-converting enzyme (ACE) inhibitors produce hemodynamic and symptomatic benefits in patients with CHF, but there is still controversy about the optimal dose in this clinical setting.


METHODS
Two hundred and forty-eight patients with advanced CHF (age 56.3+/-12 years) were randomized to receive a maximal tolerated dose of enalapril, up to 20 mg/day in group 1 (mean dose achieved 17.9+/-4.3 mg/day, n = 122) and 60 mg/day in group 2 (mean dose achieved 42+/-19.3 mg/day, n = 126).


RESULTS
At enrollment, patients in group 1 were in New York Heart Association (NYHA) functional class 2.6+/-0.7 and had a mean systolic blood pressure (SBP) of 117+/-18 mm Hg, a mean heart rate (HR) of 85+/-16 beats/min and a left ventricular ejection fraction (LVEF) of 20.0+/-9.8%. In group 2, patients were in NYHA class 2.6+/-0.7; their SBP was 118+/-17 mm Hg, HR 83+/-15 beats/min and LVEF 18.8+/-8.1%. There were no significant differences in these characteristics between the two groups of patients at enrollment. After 12 months of follow-up, 22 (18%) of 122 patients in group 1 and 23 (18%) of 126 patients in group 2 had died (p = 0.995, with 80% power of the study to detect a delta difference of 13%). The NYHA class was the same (1.9+/-0.7) in both groups; SBP was 111+/-16 and 111+/-17 mm Hg, HR 77+/-12 and 79+/-13 beats/min and LVEF 31+/-19% and 30+/-12% in groups 1 and 2, respectively. These differences were not statistically significant. The study had a power of 80% to detect (p = 0.05) the following changes: 13% in death rate, 0.25 units in NYHA class, 6 mm Hg in SBP, 5 beats/min in HR and 6% in LVEF.


CONCLUSIONS
No significant differences were found in survival and clinical and hemodynamic variables between patients receiving standard and those receiving high doses of enalapril.
Nanas
J N
JN
University of Athens School of Medicine, Department of Clinical Therapeutics, Alexandra Hospital, Greece.
Alexopoulos
G
G
Anastasiou-Nana
M I
MI
Karidis
K
K
Tirologos
A
A
Zobolos
S
S
Pirgakis
V
V
Anthopoulos
L
L
Sideris
D
D
Stamatelopoulos
S F
SF
Moulopoulos
S D
SD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D004656:Enalapril / Q000008:administration & dosage*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril