title: Carvedilol alone or in combination with digoxin for the management of atrial fibrillation in patients with heart failure?
abstract: OBJECTIVE
  This study examined the relative merits of digoxin, carvedilol, and their combination for the management of patients with atrial fibrillation (AF) and heart failure (HF).
  
  
  BACKGROUND
  In patients with AF and HF, both digoxin and beta-blockers reduce the ventricular rate, and both may improve symptoms, but only beta-blockers have been shown to improve prognosis. If combined therapy is not superior to beta-blockers alone, treatment of patients with HF and AF could be simplified by stopping digoxin.
  
  
  METHODS
  We enrolled 47 patients (29 males; mean age 68 years) with persistent AF and HF (mean left ventricular ejection fraction [LVEF] 24%) in a randomized, double-blinded, placebo-controlled study. In the first phase of the study, digoxin was compared with the combination of digoxin and carvedilol (four months). In the second phase, digoxin was withdrawn in a double-blinded manner in the carvedilol-treated arm, thus allowing a comparison between digoxin and carvedilol (six months). Investigations were undertaken at baseline and at the end of each phase.
  
  
  RESULTS
  Compared with digoxin alone, combination therapy lowered the ventricular rate on 24-h ambulatory electrocardiographic monitoring (p < 0.0001) and during submaximal exercise (p < 0.05), whereas LVEF (p < 0.05) and symptom score (p < 0.05) improved. In phase 2, there was no significant difference between digoxin alone and carvedilol alone in any variable. The mean ventricular rate rose and LVEF fell when patients switched from combination therapy to carvedilol alone. Six-minute walk distance was not significantly influenced by any therapy.
  
  
  CONCLUSIONS
  The combination of carvedilol and digoxin appears generally superior to either carvedilol or digoxin alone in the management of AF in patients with HF.
authors.affiliation: Academic Unit of Cardiology, University of Hull, Kingston-Upon-Hull, United Kingdom.
authors.forename: Aleem U
authors.initials: AU
authors.lastname: Khand
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Rankin
authors.forename: William
authors.initials: W
authors.lastname: Martin
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Taylor
authors.forename: Islay
authors.initials: I
authors.lastname: Gemmell
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D000081005:Cyclohexane Monoterpenes; D004077:Digoxin / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015716:Electrocardiography, Ambulatory; D005080:Exercise Test; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D039821:Monoterpenes / Q000008:administration & dosage*
chemical_list: D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D000081005:Cyclohexane Monoterpenes; D039821:Monoterpenes; D004077:Digoxin; C075856:carveol