Effects of intravenous dofetilide on induction of atrioventricular re-entrant tachycardia.
OBJECTIVE
To assess the efficacy and safety of intravenous dofetilide in preventing induction of atrioventricular re-entrant tachycardia.


METHODS
A multicentre, open, dose ranging trial. Fifty one patients with electrically inducible atrioventricular re-entrant tachycardia were allocated to one of five doses of dofetilide (1.5, 3, 6, 9, and 15 microgram/kg), two thirds of the dofetilide dose being given over a 15 minute loading period and the remainder over a 45 minute maintenance period.


METHODS
Responders were defined as patients in whom dofetilide prevented reinduction of atrioventricular re-entrant tachycardia at the end of the infusion.


RESULTS
Intravenous dofetilide had no effect on tachycardia inducibility at the two lower doses (1.5 and 3 microgram/kg) but prevented the reinduction of tachycardia at the three higher doses (6, 9, and 15 microgram/kg) at a rate of 36% (11/31). There was a clear relation between plasma dofetilide concentrations and efficacy (p = 0.009). In non-responders, dofetilide increased the cycle length of induced atrioventricular re-entrant tachycardia. Dofetilide increased the atrial and ventricular effective refractory periods, as well as the antegrade and retrograde effective refractory period of the accessory pathway. Treatment related side effects were reported in four patients, one with a new sustained incessant supraventricular tachycardia.


CONCLUSIONS
Dofetilide shows promise as an agent for the prevention of atrioventricular re-entrant tachycardia in patients without structural heart disease.
Cobbe
S M
SM
Department of Medical Cardiology, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER, UK. stuart.cobbe@clinmed.gla.ac.uk
Campbell
R W
RW
Camm
A J
AJ
Nathan
A W
AW
Rowland
E
E
Bloch-Thomsen
P E
PE
Møller
M
M
Jordaens
L
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010627:Phenethylamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013611:Tachycardia, Atrioventricular Nodal Reentry / Q000188:drug therapy*; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D013449:Sulfonamides; C063533:dofetilide