Dofetilide, a New Class III Antiarrhythmic Agent

Dofetilide is a new antiarrhythmic agent recently approved for conversion and maintenance of sinus rhythm in patients with atrial fibrillation (AF) and atrial flutter (AFl). It is a class III antiarrhythmic that works by selectively blocking the rapid component of the delayed rectifier outward potassium current. Dofetilide prolongs the effective refractory period in accessory pathways, both anterograde and retrograde. This can be seen on the electrocardiogram through a dose-dependent prolongation of the QT and QTc intervals, with parallel increases in ventricular refractoriness. Approximately 80% of drug is excreted in urine, so dosing must be based on creatinine clearance. The elimination half-life is approximately 10 hours. In clinical trials 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 converted within 24-36 hours. Dofetilide has a favorable risk:benefit profile. Torsades 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 of 3 days for creatinine clearance measurements, continuous electrocardiographic monitoring, and cardiac resuscitation, if necessary.