Antiarrhythmic effects of ranolazine used both alone for prevention of atrial fibrillation and as an add-on to intravenous amiodarone for its pharmacological cardioversion: a meta-analysis.

INTRODUCTION: Recent evidence from relatively small randomized controlled trials would seem to support a useful role of ranolazine for the prevention and treatment of atrial fibrillation (AF). The present study is aimed at providing information about the possible beneficial anti-arrhythmic properties of ranolazine. In particular, the meta-analysis carried out in this study focuses on the application of ranolazine to prophylaxis and treatment of atrial fibrillation.

EVIDENCE ACQUISITION: Both methods randomized controlled trials (RCTs) and non-randomized observational studies concerning the effects of ranolazine on AF were included in the meta-analysis. In each of the considered studies, a comparison was made between a group of patients taking ranolazine and a second group treated instead with another antiarrhythmic therapy, or assigned to placebo. Efficacy outcomes were the risk of new-onset AF, the probability of conversion to sinus rhythm of patients with recent occurrence (≤48 h) of AF and the time to conversion to sinus rhythm. Safety endpoints were death, adverse events, QTc prolongation and hypotension.

EVIDENCE SYNTHESIS: Ten studies (8 RCTs and 2 nonrandomized observational studies) were gathered on the whole. Ranolazine was effective in preventing the occurrence of AF when compared to controls (RR=0.60; 95% CI: 0.43-0.83; P=0.002). Subgroup analysis showed a more pronounced preventive effect of ranolazine against AF in the postoperative setting of coronary artery bypass grafting (CABG) surgery (RR=0.39; 95% CI: 0.18-0.83; P=0.02) when compared to non-postoperative AF (RR=0.76; 95% CI: 0.63-0.92; P=0.04). Ranolazine enhanced the chances of successful cardioversion when added to intravenous amiodarone compared to amiodarone alone (RR 1.18; 95% CI: 1.05-1.33; P=0.004) and significantly decreased the time to cardioversion (SMD= -10.35 h; 95% CI: -18.13 hours to -2.57 hours; P<0.001). Overall risks of death, adverse events, and QTc prolongation were shown to be similar in the comparison between patients treated with ranolazine and controls.

CONCLUSIONS: Ranolazine given orally at appropriate doses showed the property to significantly quicken the conversion of AF to sinus rhythm when combined with the IV amiodarone, compared to IV amiodarone alone. Furthermore, in patients in sinus rhythm, ranolazine proved to reduce the frequency of new onset AF as well as of its recurrences, especially in patients undergone CABG surgery, known to be at high risk of developing postoperative AF. In addition, ranolazine use seems to be safe and associated with relatively few adverse events.