Ranolazine plus amiodarone for conversion of paroxysmal atrial fibrillation

Abstract

Background: In experimental models, ranolazine exerts a synergistic effect which enhances amiodarone's potential to suppress atrial fibrillation (AF). The clinical effect of ranolazine added to amiodarone for AF conversion has only undergone minimal investigation. Purpose(s): We compared the safety and effectiveness of ranolazine plus amiodarone versus amiodarone alone for conversion of paroxysmal AF. Method(s): We prospectively enrolled all consecutive patients with paroxysmal AF who were eligible for pharmacologic cardioversion. Exclusion criteria were QTc>440msec, hepatic, renal, or thyroid disorders, acute coronary syndrome, prior use of ranolazine, and use of strong CYP3A inhibitors which could affect ranolazine's metabolism. Patients were randomized to either iv amiodarone alone (loading dose of 5md/kg followed by a maintenance dose of 50mg/h for 24h), or to the combination of iv amiodarone plus a single oral dose of ranolazine 1500mg. Patients remained on continuous ECG monitoring. We measured the time to conversion to sinus rhythm, and the proportion of patients with AF conversion within 12h and within 24h. Result(s): 72 patients were enrolled (mean age 59+/-7 years): 35 in the amiodarone-only group and 37 in the amiodarone plus ranolazine combination group. The two groups did not differ in terms of clinical characteristics and left atrium diameter. Time to conversion was shorter in the combination group compared with the amiodarone-only group (8.4+/-3.8h vs. 15.1+/-4.8 h; p<0.001). Conversion was achieved in more patients in the combination group as compared to the amiodarone-only group (57% vs. 20% at 12h, respectively, p=0.001; and 86% vs. 68% at 24h, respectively, p=0.07). There were no cases of excessive QT prolongation (>550msec) and no proarrhythmic events in either treatment group. Conclusion(s): The addition of ranolazine to standard amiodarone treatment is safe, and it leads to faster conversion of paroxysmal AF. Consistent with substantial preclinical research on ranolazine's AF-suppressing potential, the present clinical study demonstrates a synergistic effect of ranolazine and amiodarone for conversion of paroxysmal AF.