Ranolazine as a Promising Treatment Option for Atrial Fibrillation: Electrophysiologic Mechanisms, Experimental Evidence, and Clinical Implications

Currently available agents for pharmacologic management of atrial fibrillation (AF) are limited by their suboptimal efficacy and nonnegligible proarrhythmic risk. Ranolazine (RN) is a novel antianginal agent with increasingly appreciated antiarrhythmic properties that can suppress ventricular and supraventricular arrhythmias including AF. In this review, we describe the electrophysiological properties of RN, focusing on atrial-selective inhibition of a number of ion channels implicated in the development of AF, particularly the sodium current. We further summarize evidence from experimental studies that demonstrate a potent AF-suppressing effect of RN, alone or in combination with other antiarrhythmic drugs. Of clinical relevance, we present growing evidence from preliminary clinical investigations indicating the safety and efficacy of RN for prevention and treatment of AF in various clinical settings including prevention of AF in patients with acute coronary syndromes, prevention and conversion of postoperative AF after surgical coronary revascularization, sinus rhythm maintenance in drug-resistant recurrent AF, and facilitating of electrical or pharmacological cardioversion in cardioversion-resistant patients. While current experimental and clinical evidence points to RN as a potentially promising agent for suppression of AF, well-designed, large-scale trials will be required before RN can be considered for pharmacological treatment of AF in clinical practice.