Drug Evaluation Cardiovascular & Renal: Ibutilide fumarate: a new class III agent for termination of atrial fibrillation and atrial flutter

Ibutilide fumarate (Corver™, Pharmacia & Upjohn Company, Kalamazoo, MI, USA) is a novel class III methanesulfonamide antiarrhythmic agent clinically indicated for the rapid termination of atrial fibrillation and atrial flutter. This agent prolongs atrial and ventricular refractoriness and action potential duration. Ibutilide's mechanism of action is controversial, but may include potentiation of a slow inward Na+ current and inhibition of an outward K+ current (Ikr). Activation of an outward K+ current at high concentrations has also been reported. Ibutilide has no significant effects on cardiovascular autonomic function, myocardial contractility or systemic haemodynamics and has minimal effects on myocardial conduction velocity except at high concentrations. In large, randomised, placebo-controlled clinical trials, ibutilide produces arrhythmia termination in 29 - 31% of patients with atrial fibrillation and 36 - 63% of patients with atrial flutter. Conversion appears more likely for arrhythmias of shorter duration. Preliminary data suggest that ibutilide may prevent inducible ventricular tachycardia in 44% of patients, and, in animal models, ibutilide appears to reduce the energy requirements for ventricular defibrillation. In clinical studies, ibutilide is associated with sustained polymorphic ventricular tachycardia in 1.7% of patients. Heart block (1.5%), hypotension (2.0%), and bradycardia (1.2%) are uncommon.