Clinical differences between the newer antiarrhythmic agents.

In the light of studies demonstrating the serious safety problems of antiarrhythmic agents with class I activity, research and development efforts have focused largely on drugs with a class III mechanism of action. Most of the newer agents target the rapid component of the delayed rectifier potassium current (I(Kr)). In the case of dofetilide, the mechanism of action is relatively pure, with single I(Kr) channel blocking activity. Other agents have a wider spectrum of activity. Azimilide blocks both the rapid I(Kr) and slow I(Ks) potassium currents and ibutilide also augments the inward sodium current. Clinical investigation of these agents has shown them to be effective antiarrhythmic drugs with a number of advantages over existing agents, particularly in terms of safety. Dronedarone and tedisamil also have multichannel blocking actions and are in earlier stages of clinical development. Until now, therapeutic choices have been limited and far from ideal. It is hoped that the availability of the newer class III agents will at least provide greater choice of therapy and hopefully will bring us closer to therapeutic ideals in the management of arrhythmia.