Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: 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 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 dat were analyzed by ANOV 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 synergistic effect on the AV node. The dat provides basis for testing the effects of chronic suppression of diurnal fluctuations of VR on left atrial and ventricular function in CAF.