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CLINICAL STUDY: HEART FAILURE

Outcome of patients with congestive heart failure treated with standard versus high doses of enalapril: a multicenter study

John N. Nanas, MD, PhD^*, George Alexopoulos, MD^*, Maria I. Anastasiou-Nana, MD^*, Konstantinos Karidis, MD, Argiris Tirologos, MD, Spyridon Zobolos, MD^||, Vlasios Pirgakis, MD, Labros Anthopoulos, MD, PhD^#, Dimitrios Sideris, MD, PhD^**, Stamatis F. Stamatelopoulos, MD, PhD^*, Spyridon D. Moulopoulos, MD, PhD^* for the High Enalapril Dose Study Group

^* University of Athens School of Medicine, Department of Clinical Therapeutics, Alexandra Hospital, Athens, Greece
Sotiria Hospital, Athens, Greece
Kavala Hospital, Kavala, Greece
^|| Kalamata Hospital, Kalamata, Greece
Korinthos Hospital, Korinthos, Greece
^# Evagelismos Hospital, Athens, Greece
^** University of Ioannina, Department of Cardiology, Ioannina, Greece

Manuscript received March 13, 2000; revised manuscript received July 11, 2000, accepted August 24, 2000.

Reprint requests and correspondence: Dr. John N. Nanas, Makedonias 24, GR 104 33 Athens, Greece

OBJECTIVES

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.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ATLAS = Assessment of Treatment with Lisinopril And Survival study   CHF = congestive heart failure   CONSENSUS = COoperative North Scandinavian ENalapril SUrvival Study   HR = heart rate   LVEF = left ventricular ejection fraction   NYHA = New York Heart Association   SBP = systolic blood pressure   SOLVD = Studies Of Left Ventricular Dysfunction   V-HeFT = Veterans Administration Vasodilator Heart Failure Trial

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