CLINICAL RESEARCH: HEART FAILURE
Carvedilol alone or in combination with digoxin for the management of atrial fibrillation in patients with heart failure?
Aleem U. Khand, MD, MRCP ,
Andrew C. Rankin, MD, MRCP*,
William Martin, PhD*,
Jacqueline Taylor, MBChB, MRCP*,
Islay Gemmell, MSc, PhD and
John G. F. Cleland, MD, MRCP, FACC,*
* Department of Cardiology, Glasgow Royal Infirmary, Glasgow, Scotland, United Kingdom
Academic Unit of Cardiology, University of Hull, Kingston-upon-Hull, United Kingdom
Social and Public Health Sciences Unit, University of Glasgow, Glasgow, Scotland, United Kingdom
Manuscript received April 25, 2003;
revised manuscript received July 2, 2003,
accepted July 7, 2003.
* Reprint requests and correspondence: Prof. John G. F. Cleland, Academic Unit of Cardiology, Castlehill Hospital, Castlehill Road, Kingston-Upon-Hull, United Kingdom, HU165JQ.
J.G.Cleland{at}medschool.hull.ac.uk
OBJECTIVES: This study examined the relative merits of digoxin, carvedilol, and their combination for the management of patients with atrial fibrillation (AF) and heart failure (HF).
BACKGROUND: In patients with AF and HF, both digoxin and beta-blockers reduce the ventricular rate, and both may improve symptoms, but only beta-blockers have been shown to improve prognosis. If combined therapy is not superior to beta-blockers alone, treatment of patients with HF and AF could be simplified by stopping digoxin.
METHODS: We enrolled 47 patients (29 males; mean age 68 years) with persistent AF and HF (mean left ventricular ejection fraction [LVEF] 24%) in a randomized, double-blinded, placebo-controlled study. In the first phase of the study, digoxin was compared with the combination of digoxin and carvedilol (four months). In the second phase, digoxin was withdrawn in a double-blinded manner in the carvedilol-treated arm, thus allowing a comparison between digoxin and carvedilol (six months). Investigations were undertaken at baseline and at the end of each phase.
RESULTS: Compared with digoxin alone, combination therapy lowered the ventricular rate on 24-h ambulatory electrocardiographic monitoring (p < 0.0001) and during submaximal exercise (p < 0.05), whereas LVEF (p < 0.05) and symptom score (p < 0.05) improved. In phase 2, there was no significant difference between digoxin alone and carvedilol alone in any variable. The mean ventricular rate rose and LVEF fell when patients switched from combination therapy to carvedilol alone. Six-minute walk distance was not significantly influenced by any therapy.
CONCLUSIONS: The combination of carvedilol and digoxin appears generally superior to either carvedilol or digoxin alone in the management of AF in patients with HF.
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Abbreviations and Acronyms
| | AF | = atrial fibrillation | | BNP | = brain natriuretic peptide | | BP | = blood pressure | | ECG | = electrocardiogram/electrocardiographic | | HF | = heart failure | | HR | = heart rate | | LV | = left ventricular | | LVEF | = left ventricular ejection fraction | | NYHA | = New York Heart Association | | RPP | = rate-pressure product |
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