Ranolazine as Antiarrhythmic Agent

Abstract

Ranolazine which has been approved for use an anti-anginal agent has been shown to have anti-arrhythmic properties both in experimental and clinical studies. Several case studies have shown the use of ranolazine in the treatment of atrial fibrillation, some even as a ‘pill in the pocket’ approach. MERLIN-TIMI 36, a randomized study of acute coronary syndrome, showed lower incidence of ventricular arrhythmias in the ranolazine arm. The most important anti-arrhythmic mechanism of of ranolazine is thought to be mediated by atrial-selective inhibition of peak sodium current (INaL) and inhibition of late INa in both atria and ventricles. The recent reclassification of anti-arrhythmic agents has designated drugs with this action in Class Id. There is clinical and experimental evidence for the potential use of ranolazine in congenital long QT syndrome 3. The recent RAID trial, a randomized evaluation of ranolazine in high risk patients with implantable cardioverter defibrillator and either ischemic or non-ischemic cardiomyopathy showed a marginally significant reduction of recurrent ventricular tachycardia and fibrillation. The potential risk of ranolazine-induced torsade de pointes in view of mild prolongation of QT interval has not been well confirmed, with only a single case report suggesting possible association. But the patient had other confounding factors including treatment with fluoxetine, amiodarone and diuretics causing hypokalemia and hypomagnesemia which are well known to cause torsade de pointes.