Carvedilol alone or in combination with digoxin for the management of atrial fibrillation in patients with heart failure?
Open accessAbstract
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 In the second phase, digoxin was withdrawn in a double-blinded manner in the carvedilol-treated arm, thus allowing a comparison between digoxin and carvedilol (six months).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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Comparisons with other rate control therapies are based on small, short-duration studies that identify no or marginal differences in exercise capacity, quality of life, or LVEF compared to digoxin.
“Comparisons with other rate control therapies are based on small, short-duration studies that identify no or marginal differences in exercise capacity, quality of life, or LVEF compared to digoxin.526,[554][555][556][557][558]”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [554]
In a crossover mechanistic trial of 47 patients with HFrEF and AF, there were no differences in heart rate, blood pressure, walking distance, or LVEF between carvedilol and digoxin.
“In a crossover mechanistic trial of 47 patients with HFrEF and AF, there were no differences in heart rate, blood pressure, walking distance, or LVEF between carvedilol and digoxin, although beta-blockers did result in higher B-type natriuretic peptide levels, combination carvedilol/digoxin improved LVEF, and digoxin withdrawal reduced LVEF.554”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [554]
In the same trial, beta-blockers resulted in higher B-type natriuretic peptide levels.
“In a crossover mechanistic trial of 47 patients with HFrEF and AF, there were no differences in heart rate, blood pressure, walking distance, or LVEF between carvedilol and digoxin, although beta-blockers did result in higher B-type natriuretic peptide levels, combination carvedilol/digoxin improved LVEF, and digoxin withdrawal reduced LVEF.554”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [554]
In the same trial, combination carvedilol/digoxin improved LVEF.
“In a crossover mechanistic trial of 47 patients with HFrEF and AF, there were no differences in heart rate, blood pressure, walking distance, or LVEF between carvedilol and digoxin, although beta-blockers did result in higher B-type natriuretic peptide levels, combination carvedilol/digoxin improved LVEF, and digoxin withdrawal reduced LVEF.554”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [554]
In the same trial, digoxin withdrawal reduced LVEF.
“In a crossover mechanistic trial of 47 patients with HFrEF and AF, there were no differences in heart rate, blood pressure, walking distance, or LVEF between carvedilol and digoxin, although beta-blockers did result in higher B-type natriuretic peptide levels, combination carvedilol/digoxin improved LVEF, and digoxin withdrawal reduced LVEF.554”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [554]
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- Authors
- Khand, A. U., Rankin, A. C., Martin, W., Taylor, J., Gemmell, I., & Cleland, J. G. F.
- Affiliations
- University of Hull (GB)
- Glasgow Royal Infirmary (GB)
- MRC/CSO Social and Public Health Sciences Unit (GB)
- Corresponding author
- Cleland, John G.F
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2003-12
- Volume
- 42
- Issue
- 11
- Pages
- 1944-1951
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2138396513
- Cited by
- 271
- References
- 29
- Citations by year
- 2026: 9 · 2025: 5 · 2024: 13 · 2023: 7 · 2022: 5 · 2021: 12 · 2020: 12 · 2019: 6 · 2018: 8 · 2017: 13 · 2016: 18 · 2015: 17 · 2014: 13 · 2013: 19 · 2012: 12
- FWCI
- 9.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
- Keywords
- carvedilol, digoxin, atrial fibrillation, heart failure, combination therapy, beta-blockers, ventricular rate control, left ventricular ejection fraction, symptom scores
- MeSH terms
- Cyclohexane Monoterpenes, Adrenergic beta-Antagonists, Aged, Anti-Arrhythmia Agents, Atrial Fibrillation, Digoxin, Double-Blind Method, Drug Therapy, Combination, Exercise Test, Female, Heart Failure, Humans, Male, Electrocardiography, Ambulatory, Monoterpenes
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