Dofetilide: first of a new generation of class III agents

Dofetilide (Pfizer, Sandwich, Kent, UK) is a novel, highly specific class III methanesulfonanilide anti-arrhythmic drug. At nanomolar concentrations this agent prolongs both the atrial and ventricular effective refractory periods and action potential duration. Dofetilide's mechanism of action relies on potent blockade of the rapidly activating, inwardly rectifying component of the delayed rectifier potassium current (Ikr), the main current responsible for cardiac repolarisation. Dofetilide does not appear to interact with other cardiac ionic channels, and this explains its minimal effects upon conduction velocity, myocardial contractility and systemic haemodynamics. Dofetilide's mechanism of action makes it suitable for the termination of supraventricular and ventricular tachyarrhythmias. Small scale clinical trials have provided encouraging results, with preliminary data confirming its efficacy in the termination of atrial fibrillation and atrial flutter, and in increasing the electrical threshold for inducible ventricular tachycardia/fibrillation. The results of large scale, randomised, placebo-controlled trials are awaited in order to establish dofetilide's role in clinical practice. Due to its very specific mode of action, dofetilide has very few systemic side-effects. Dofetilide represents a novel and promising new class III agent.