Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: a crossover open-label study of five drug regimens

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 r...

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Bibliographic Details
Published in:Journal of the American College of Cardiology 1999-02, Vol.33 (2), p.304-310
Main Authors: Farshi, Ramin, Kistner, Deborah, Sarma, Jonnalagedda S.M, Longmate, Jeffrey A, Singh, Bramah N
Format: Article
Language:English
Subjects:
Aged
Anti-Arrhythmia Agents - therapeutic use
Atenolol - therapeutic use
Atrial Fibrillation - drug therapy
Atrial Fibrillation - physiopathology
Biological and medical sciences
Calcium Channel Blockers - therapeutic use
Cardiac dysrhythmias
Cardiology. Vascular system
Circadian Rhythm - physiology
Cross-Over Studies
Digoxin - therapeutic use
Diltiazem - therapeutic use
Drug Therapy, Combination
Electrocardiography, Ambulatory
Exercise - physiology
Female
Follow-Up Studies
Heart
Heart Rate
Heart Ventricles - drug effects
Heart Ventricles - physiopathology
Humans
Male
Medical sciences
Middle Aged
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Summary: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.
ISSN:0735-1097
1558-3597
DOI:10.1016/S0735-1097(98)00561-0