Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: a crossover open-label study of five drug regimens
Open accessAbstract
Objectives We compared the effects of five pharmacologic regimens on the circadian rhythm and exercise-induced changes of ventricular rate (VR) in patients with chronic atrial fibrillation (CAF).Background Systematic comparison of standardized drug regimens on 24 h VR control in CAF have not been reported.Methods In 12 patients (11 male, 69+/-6 yr) with CAF, the effects on VR by 5 standardized daily regimens: 1) 0.25 mg digoxin, 2) 240 mg diltiazem-CD, 3) 50 mg atenolol, 4) 0.25 mg digoxin + 240 mg diltiazem-CD, and 5) 0.25 mg digoxin + 50 mg atenolol; were studied after 2 week treatment assigned in random order. The VR data were analyzed by ANOVA with repeated measures. The circadian phase differences were evaluated by cosinor analysis.Results The 24-h mean (+/-SD) values of VR (bpm) were - digoxin: 78.9 +/- 16.3, diltiazem: 80.0+/-15.5, atenolol: 75.9+/-11.7, digoxin + diltiazem: 67.3+/-14.1 and digoxin + atenolol: 65.0+/-9.4. Circadian patterns were significant in each treatment group (p < 0.001). The VR on digoxin + atenolol was significantly lower than that on digoxin (p < 0.0001), diltiazem (p < 0.0002) and atenolol (p < 0.001). The time of peak VR on Holter was significantly delayed with regimens 3 and 5 which included atenolol (p < 0.03). During exercise, digoxin and digoxin + atenolol treatments resulted in the highest and lowest mean VR respectively. The exercise Time-VR plots of all groups were nearly parallel (p = ns). The exercise duration was similar in all treatment groups (p = ns).Conclusions This study indicates that digoxin and diltiazem, as single agents at the doses tested, are least effective for controlling ventricular rate in atrial fibrillation during daily activity. Digoxin + atenolol produced the most effective rate control reflecting a synergistic effect on the AV node. The data provides a basis for testing the effects of chronic suppression of diurnal fluctuations of VR on left atrial and ventricular function in CAF.
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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 [555]
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References 33 · Cited by 363
- Authors
- Farshi, R., Kistner, D., Sarma, J. S. M., Longmate, J. A., & Singh, B. N.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Singh, Bramah N
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 1999-02
- Volume
- 33
- Issue
- 2
- Pages
- 304-310
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2138806529
- Cited by
- 363
- References
- 33
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 11 · 2020: 8 · 2019: 4 · 2018: 6 · 2017: 6 · 2016: 15 · 2015: 8 · 2014: 18 · 2013: 14 · 2012: 16
- FWCI
- 12.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
- Keywords
- chronic atrial fibrillation, ventricular rate control, digoxin, diltiazem, atenolol, beta-blockers, calcium channel blockers, circadian rhythm, crossover design, Holter monitoring, anticoagulation, cardioversion, atrial fibrillation
- MeSH terms
- Aged, Anti-Arrhythmia Agents, Atenolol, Atrial Fibrillation, Calcium Channel Blockers, Circadian Rhythm, Digoxin, Diltiazem, Drug Therapy, Combination, Female, Follow-Up Studies, Heart Rate, Heart Ventricles, Humans, Male, Middle Aged, Exercise, Electrocardiography, Ambulatory, Cross-Over Studies
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