Dofetilide, a new class III antiarrhythmic agent

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.