title: Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group.
abstract: BACKGROUND
  Atrial fibrillation occurs frequently in patients with congestive heart failure and commonly results in clinical deterioration and hospitalization. Sinus rhythm may be maintained with antiarrhythmic drugs, but some of these drugs increase the risk of death.
  
  
  METHODS
  We studied 1518 patients with symptomatic congestive heart failure and severe left ventricular dysfunction at 34 Danish hospitals. We randomly assigned 762 patients to receive dofetilide, a novel class III antiarrhythmic agent, and 756 to receive placebo in a double-blind study. Treatment was initiated in the hospital and included three days of cardiac monitoring and dose adjustment. The primary end point was death from any cause.
  
  
  RESULTS
  During a median follow-up of 18 months, 311 patients in the dofetilide group (41 percent) and 317 patients in the placebo group (42 percent) died (hazard ratio, 0.95; 95 percent confidence interval, 0.81 to 1.11). Treatment with dofetilide significantly reduced the risk of hospitalization for worsening congestive heart failure (risk ratio, 0.75; 95 percent confidence interval, 0.63 to 0.89). Dofetilide was effective in converting atrial fibrillation to sinus rhythm. After one month, 22 of 190 patients with atrial fibrillation at base line (12 percent) had sinus rhythm restored with dofetilide, as compared with only 3 of 201 patients (1 percent) given placebo. Once sinus rhythm was restored, dofetilide was significantly more effective than placebo in maintaining sinus rhythm (hazard ratio for the recurrence of atrial fibrillation, 0.35; 95 percent confidence interval, 0.22 to 0.57; P<0.001). There were 25 cases of torsade de pointes in the dofetilide group (3.3 percent) as compared with none in the placebo group.
  
  
  CONCLUSIONS
  In patients with congestive heart failure and reduced left ventricular function, dofetilide was effective in converting atrial fibrillation, preventing its recurrence, and reducing the risk of hospitalization for worsening heart failure. Dofetilide had no effect on mortality.
authors.affiliation: Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Torp-Pedersen
authors.forename: M
authors.initials: M
authors.lastname: Møller
authors.forename: P E
authors.initials: PE
authors.lastname: Bloch-Thomsen
authors.forename: L
authors.initials: L
authors.lastname: Køber
authors.forename: E
authors.initials: E
authors.lastname: Sandøe
authors.forename: K
authors.initials: K
authors.lastname: Egstrup
authors.forename: E
authors.initials: E
authors.lastname: Agner
authors.forename: J
authors.initials: J
authors.lastname: Carlsen
authors.forename: J
authors.initials: J
authors.lastname: Videbaek
authors.forename: B
authors.initials: B
authors.lastname: Marchant
authors.forename: A J
authors.initials: AJ
authors.lastname: Camm
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D010627:Phenethylamines / Q000009:adverse effects / Q000627:therapeutic use*; D055502:Secondary Prevention; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D016171:Torsades de Pointes / Q000139:chemically induced; D018487:Ventricular Dysfunction, Left / Q000209:etiology
chemical_list: D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D013449:Sulfonamides; C063533:dofetilide