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CLINICAL STUDIES

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

Andrea Di Lenarda, MD^*, Gastone Sabbadini, MD, Luca Salvatore, MD^*, Gianfranco Sinagra, MD^*, Luisa Mestroni, MD, FACC, Bruno Pinamonti, MD^*, Dario Gregori, PhD, Fulvio Ciani, MD^||, Aureo Muzzi, MD^*, Silvio Klugmann, MD^*, Fulvio Camerini, MD^* The Heart-Muscle Disease Study Group

^* Department of Cardiology, Ospedale Maggiore, Trieste, Italy
Department of Internal Medicine and Geriatrics, University of Trieste, Trieste, Italy
International Center for Genetic Engineering and Biotechnologies, Area Science Park, Trieste, Italy
Department of Statistics, University of Trieste, Trieste, Italy
^|| Respiratory Physiopathology Service, Ospedale Santorio, Trieste, Italy

Manuscript received September 25, 1998; revised manuscript received January 27, 1999, accepted February 25, 1999.

Reprint requests and correspondence: Dr. Andrea Di Lenarda, MD, Department of Cardiology, Ospedale Maggiore, Piazza Ospedale 1, 34100 Trieste, Italy
dilenar{at}uts.univ.trieste.it

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 and Acronyms   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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