Efficacy and safety of intravenously administered dofetilide in acute termination of atrial fibrillation and flutter: a multicenter, randomized, double-blind, placebo-controlled trial. Danish Dofetilide in Atrial Fibrillation and Flutter Study Group.
BACKGROUND
This study was designed to assess the efficacy and safety of intravenous dofetilide in acute termination of atrial fibrillation (AF) and flutter (AFL). Dofetilide, an investigational class III antiarrhythmic agent, selectively inhibits the rapid component of the delayed rectifier potassium current, thus prolonging the effective refractory period and duration of the action potential. Dofetilide can be administered intravenously and has a rapid onset of electrophysiologic action.


RESULTS
Ninety-six patients with AF (n = 79) or AFL (n = 17) with a median arrhythmia duration of 62 days (range 1 to 180) were randomized to placebo (n = 30) or 8 micrograms/kg IV dofetilide (n = 66) over 30 minutes. Conversion was defined as termination of the atrial arrhythmia within 3 hours from the start of infusion. The conversion rate was 30.3% after dofetilide and 3.3% after placebo (P <.006). Conversion rate was higher in AFL than in AF: 64% versus 24% (P =. 012). In nonconverters, there was no statistically significant difference between the change in heart rate among the dofetilide-treated compared with the placebo-treated patients (P =. 42). Torsade de pointes ventricular tachycardia developed in 2 patients (3%). In both patients, drug infusion was discontinued before the event because of prolongation of the QT interval.


CONCLUSIONS
Intravenous dofetilide is effective in acute termination of AF and AFL of medium duration, with a particularly high efficacy rate in AFL. A small but serious risk of proarrhythmia must be anticipated.
Nørgaard
B L
BL
Aarhus University Hospital, Aarhus, Denmark.
Wachtell
K
K
Christensen
P D
PD
Madsen
B
B
Johansen
J B
JB
Christiansen
E H
EH
Graff
O
O
Simonsen
E H
EH
D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D001282:Atrial Flutter / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D003718:Denmark; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010627:Phenethylamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D010919:Placebos; D026902:Potassium Channel Blockers; D011446:Prospective Studies; D012449:Safety; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D010919:Placebos; D026902:Potassium Channel Blockers; D013449:Sulfonamides; C063533:dofetilide