Dofetilide is a new antiarrhythmic agent recently approved for conversion a
nd maintenance of sinus rhythm in patients with atrial fibrillation (AF) an
d atrial flutter (AFl). It is a class III antiarrhythmic that works by sele
ctively blocking the rapid component of the delayed rectifier outward potas
sium current. Dofetilide prolongs the effective refractory period in access
ory pathways, both anterograde and retrograde. This can be seen on the elec
trocardiogram through a dose-dependent prolongation of the QT and QTc inter
vals, with parallel increases in ventricular refractoriness. Approximately
80% of drug is excreted in urine, so dosing must be based on creatinine cle
arance. The elimination half-life is approximately 10 hours. In clinical tr
ials dofetilide was superior to flecainide in converting patients with AFl
to normal sinus rhythm (NSR; 70% vs 9%, p<0.01). It also was more effective
than sotalol in converting patients with both AF and AFl to NSR (29% vs 6%
, p<0.05) and maintaining them in NSR for up to 1 year. Most patients conve
rted within 24-36 hours. Dofetilide has a favorable risk:benefit profile. T
orsades de pointes is the most serious side effect; it occurs in 0.3-10.5%
of patients and is dose related. To minimize the risk of induced arrhythmia
, patients who start or restart the drug should be hospitalized a minimum o
f 3 days for creatinine clearance measurements, continuous electrocardiogra
phic monitoring, and cardiac resuscitation, if necessary.