Dofetilide: a class III-specific antiarrhythmic agent

OBJECTIVE: To review published reports on the pharmacology and clinical use of dofetilide in the management of cardiac dysrhythmias. DATA SOURCES: A MEDLINE search (January 1966-June 1999) was performed using dofetilide and UK-68,798 as key words. English-language articles were identified, and the references of these articles were used to further identify pertinent articles. STUDY SELECTION: All acquired studies and reviews discussing the pharmacology, pharmacokinetics, chemistry, and clinical efficacy of dofetilide were reviewed. DATA EXTRACTION: Articles were selected based on quality of review of the pharmacology and clinical use of dofetilide. Given the paucity of data on the clinical pharmacology and use of dofetilide, most articles obtained were used, including abstracts when full reports were not available. DATA SYNTHESIS: Dofetilide is a relatively specific class III antiarrhythmic agent. It increases action potential duration and effective refractory period without impacting conduction velocity. These actions of dofetilide are explained by its ability to inhibit the rapid component of the delayed, outward-rectifying potassium current, thus blocking the efflux of potassium during repolarization. Introductory investigations suggest that dofetilide may be of use in treating and preventing atrial dysrhythmias such as atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia. Dofetilide may also have a role in preventing ventricular tachycardia from occurring. Some data also suggest that dofetilide may improve the morbidity of heart failure patients. Currently, the most troublesome adverse effect of dofetilide is its propensity to induce ventricular proarrhythmias, especially torsade de pointes. CONCLUSIONS: Based on the data currently available, dofetilide should have a role in the pharmacotherapy of cardiac dysrhythmias, especially those of atrial origin. More data on its efficacy and tolerability are needed, however, to fully delineate dofetilide's role amid currently available antiarrhythmic agents.