Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol. The Heart-Muscle Disease Study Group.
OBJECTIVE
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 < or =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.
Di Lenarda
A
A
Department of Cardiology, Ospedale Maggiore, Trieste, Italy. dilenar@uts.univ.trieste.it
Sabbadini
G
G
Salvatore
L
L
Sinagra
G
G
Mestroni
L
L
Pinamonti
B
B
Gregori
D
D
Ciani
F
F
Muzzi
A
A
Klugmann
S
S
Camerini
F
F
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002227:Carbazoles / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000077261:Carvedilol; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D015150:Echocardiography, Doppler; D015716:Electrocardiography, Ambulatory; D005080:Exercise Test; D005500:Follow-Up Studies; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008790:Metoprolol / Q000627:therapeutic use*; D009200:Myocardial Contraction / Q000187:drug effects; D010101:Oxygen Consumption; D011412:Propanolamines / Q000627:therapeutic use*; D011788:Quality of Life; D012189:Retrospective Studies; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol