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

J Am Coll Cardiol. 1999 Feb;33(2):304-10. doi: 10.1016/s0735-1097(98)00561-0.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Arrhythmia Agents / therapeutic use*
  • Atenolol / therapeutic use
  • Atrial Fibrillation / drug therapy
  • Atrial Fibrillation / physiopathology*
  • Calcium Channel Blockers / therapeutic use*
  • Circadian Rhythm / physiology*
  • Cross-Over Studies
  • Digoxin / therapeutic use
  • Diltiazem / therapeutic use
  • Drug Therapy, Combination
  • Electrocardiography, Ambulatory
  • Exercise / physiology*
  • Female
  • Follow-Up Studies
  • Heart Rate*
  • Heart Ventricles / drug effects
  • Heart Ventricles / physiopathology*
  • Humans
  • Male
  • Middle Aged


  • Anti-Arrhythmia Agents
  • Calcium Channel Blockers
  • Atenolol
  • Digoxin
  • Diltiazem