title: Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: a crossover open-label study of five drug regimens.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Cardiology, West Los Angeles VA Medical Center, UCLA School of Medicine, California 90073, USA.
authors.forename: R
authors.initials: R
authors.lastname: Farshi
authors.forename: D
authors.initials: D
authors.lastname: Kistner
authors.forename: J S
authors.initials: JS
authors.lastname: Sarma
authors.forename: J A
authors.initials: JA
authors.lastname: Longmate
authors.forename: B N
authors.initials: BN
authors.lastname: Singh
mesh_terms: D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000503:physiopathology*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002940:Circadian Rhythm / Q000502:physiology*; D018592:Cross-Over Studies; D004077:Digoxin / Q000627:therapeutic use; D004110:Diltiazem / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D015716:Electrocardiography, Ambulatory; D015444:Exercise / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged