Clinical Studies
Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol

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Abstract

OBJECTIVES

The purpose of this study was to analyze whether long-term treatment with the nonselective beta-adrenergic blocking agent carvedilol may have beneficial effects in patients with dilated cardiomyopathy (DCM), who are poor responders in terms of left ventricular (LV) function and exercise tolerance to chronic treatment with the selective beta-blocker metoprolol.

BACKGROUND

Although metoprolol has been proven to be beneficial in the majority of patients with heart failure, a subset of the remaining patients shows long-term survival without satisfactory clinical improvement.

METHODS

Thirty consecutive DCM patients with persistent LV dysfunction (ejection fraction ≤40%) and reduced exercise tolerance (peak oxygen consumption <25 ml/kg/min) despite chronic (>1 year) tailored treatment with metoprolol and angiotensin-converting enzyme inhibitors were enrolled in a 12-month, open-label, parallel trial and were randomized either to continue on metoprolol (n = 16, mean dosage 142 ± 44 mg/day) or to cross over to maximum tolerated dosage of carvedilol (n = 14, mean dosage 74 ± 23 mg/day).

RESULTS

At 12 months, patients on carvedilol, compared with those continuing on metoprolol, showed a decrease in LV dimensions (end-diastolic volume −8 ± 7 vs. +7 ± 6 ml/m2, p = 0.053; end-systolic volume −7 ± 5 vs. +6 ± 4 ml/m2, p = 0.047), an improvement in LV ejection fraction (+7 ± 3% vs. −1 ± 2%, p = 0.045), a reduction in ventricular ectopic beats (−12 ± 9 vs. +62 ± 50 n/h, p = 0.05) and couplets (−0.5 ± 0.4 vs. +1.5 ± 0.6 n/h, p = 0.048), no significant benefit on symptoms and quality of life and a negative effect on peak oxygen consumption (−0.6 ± 0.6 vs. +1.3 ± 0.5 ml/kg/min, p = 0.03).

CONCLUSIONS

In DCM patients who were poor responders to chronic metoprolol, carvedilol treatment was associated with favorable effects on LV systolic function and remodeling as well as on ventricular arrhythmias, whereas it had a negative effect on peak oxygen consumption.

Abbreviations

ACE
angiotensin-converting enzyme
CI
confidence interval
DCM
dilated cardiomyopathy
EDV
end-diastolic volume
EF
ejection fraction
ESV
end-systolic volume
LV
left ventricular
NYHA
New York Heart Association
VO2
volume of oxygen consumption

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