Ibutilide – recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation

Abstract

Ibutilide is a ‘pure’ class III antiarrhythmic drug, used intravenously against atrial flutter and fibrillation. At a cellular level it exerts two main actions: induction of a persistent Na+ current sensitive to dihydropyridine Ca2+ channel blockers and potent inhibition of the cardiac rapid delayed rectifier K⁺ current, by binding within the channel pore cavity upon channel gating. Ibutilide has been shown to terminate atrial flutter and fibrillation in animal studies, with some risk of ventricular pro-arrhythmia. Experimental models of hypertrophy/heart failure show altered sensitivity to ibutilide, with increased dispersion of repolarisation and incidence of pro-arrhythmia. Patient trials show that ibutilide is effective at terminating atrial arrhythmias when given alone, and that it can increase effectiveness and reduce energy requirements of electrical cardioversion. The risk to patients of polymorphic ventricular tachycardia necessitates careful patient selection and monitoring during and after treatment. An ibutilide analogue, trecetilide, requires further investigation but may offer a less readily metabolised and pro-arrhythmic alternative to ibutilide.

Keywords::

• animal models
• antiarrhythmic
• arrhythmia
• atrial fibrillation
• clinical trials
• HERG
• ibutilide
• polymorphic ventricular tachycardia
• trecetilide