“Ranolaziodarone”—A Synergism You Should Not Miss

Abstract

Dr. Reiffel has been an investigator for Medtronic, Janssen, and Sanofi; a consultant for Medtronic, Sanofi, Acesion, Correvio, and Amarin; and has served on a speaker’s bureau for Sanofi within the past 12 months. Address correspondence to: James A. Reiffel, MD, c/o 202 Birkdale Lane, Jupiter, FL 33458, USA. Email: [email protected]. In this issue of The Journal of Innovations in Cardiac Rhythm Management, Aidonidis et al.1 report on the effects of ranolazine and its combination with amiodarone on rapid pacing–induced reentrant atrial tachycardia in rabbits. In their study, the authors observed that, (1) in the dose given, ranolazine did not abolish the inducibility of atrial tachycardia in any of the eight rabbits studied, but did prolong its cycle length; (2) supplemental amiodarone, in the dose given, increased the atrial tachycardia cycle length further, without abolishing reinducibility; (3) the more pronounced slowing of the tachycardia with the combined regimen was associated with spontaneous termination; and (4) ranolazine prolonged atrial postrepolarization refractoriness, which was further prolonged when amiodarone was added. The authors commented on the possible clinical relevance of these observations by noting that “collectively, although these experimental data cannot be directly extrapolated to human subjects with structural heart disease, their synergistic electrophysiologic actions support the contention that a combination of ranolazine and amiodarone for the termination and prevention of sustained atrial tachycardia might be better than either of these agents alone.” While it is a big leap (or, should I say, hop) from eight rabbits to the management of atrial tachyarrhythmias in humans—including, most importantly, atrial fibrillation (AF), mankind’s most common and troublesome atrial tachyarrhythmia—the use of a combination of antiarrhythmic drugs (AADs) to treat arrhythmias in humans (and other species) is not a new concept. Moreover, neither is the use of ranolazine combined with amiodarone, or its derivative, dronedarone. In reality, AADs in combination with each other have been used for difficult-to-manage arrhythmias for decades. For example, prior to the development of the implantable cardioverter-defibrillator, patients with refractory ventricular arrhythmias were either managed with empiric amiodarone or with AADs in combination, such as quinidine plus mexiletine, with moderate success.2,3 Similarly, beyond their use to achieve added efficacy, when the tolerance of a full dose of an AAD was an issue despite its efficacy, lower-dose combinations of AADs have been tried, such as quinidine plus disopyramide, with each offsetting the other’s gastrointestinal side effects.4,5