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  • A number of clinical studies have confirmed

    2019-05-17

    A number of clinical studies have confirmed the beneficial effect of ranolazine in either mineralocorticoid receptor antagonists prevention or treatment of AF. The first strong evidence was provided by MERLIN-TIMI 36 trial [the Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST-Elevation Acute Coronary Syndrome–Thrombolysis in Myocardial Infarction] [19], which showed that ranolazine may reduce the incidence rate of paroxysmal AF in patients with non-ST elevated acute coronary syndrome, and it also reduced overall AF burden. Few more studies showed the benefit of ranolazine in pharmacological cardioversion. Fragakis et al. [20] concluded that ranolazine–amiodarone combination showed a higher rate of pharmacological cardioversion compared to amiodarone alone, suggesting a potential synergistic effect of ranolazine when added to amiodarone. In another study on pharmacological cardioversion conducted by Murdock et al. [21], patients with paroxysmal AF converted to sinus rhythm within only 6h of ranolazine administration. The HARMONY trial [22] evaluated the safety and efficacy of ranolazine–dronedarone combination in the treatment of patients having paroxysmal AF. In that trial, a significant AF mineralocorticoid receptor antagonists was observed by synergistic effect of ranolazine plus dronedarone, with a good safety profile. Another groundbreaking RAFFAELLO clinical trial [Ranolazine in Atrial Fibrillation Following an ELectricaL CardiOversion] [23] assessed the safety and efficacy of ranolazine in the prevention of AF recurrence after successful electrical cardioversion and to ascertain the most appropriate dose of ranolazine. The RAFFAELLO trial was a prospective, multicenter, randomized, double-blind, placebo-controlled parallel group phase II dose-ranging clinical study and concluded that ranolazine on 500mg and 750mg significantly reduce recurrence after successful electrical cardioversion. Although several studies have shown the effect of ranolazine in the prevention or treatment of arrhythmia, most of them were designed differently except for the studies on the prevention of AF post-cardiac surgery. Thus, we decided to perform the meta-analysis on Efficacy of Ranolazine in Preventing Atrial Fibrillation following cardiac surgery, and to the best of our knowledge, this is the first study that evaluated the effectiveness of ranolazine in preventing POAF occurrence after cardiac surgery through a meta-analysis. The finding from our study shows that the addition of ranolazine to the standard therapy reduces POAF nearly 55% compared to standard therapy alone. POAF is the most common tachyarrhythmia and frequently occurring complication following cardiac surgery. POAF can lead to severe thromboembolic complications, such as stroke. It reduces the quality of life and increases the hospitalization period. Furthermore, early POAF is the predictor of late recurrence, and hence, preventing POAF incidence is important. AF after cardiac surgery remains a challenge, and the results from currently available treatment options are unsatisfactory. Amiodarone is the most potent AAD and often used along with standard therapy to prevent AF after cardiac surgery; however, it is frequently associated with hepatic, pulmonary, and thyroid adverse events. Therefore, it is imperative to find a treatment plan to prevent the POAF. Ranolazine, an anti-ischemic medication with novel inhibitory action on late inward sodium channels within cardiomyocytes, demonstrates promising potential in AF prevention. Several recent studies have shown the benefit of ranolazine in POAF prevention in patients undergoing cardiac surgery. Moreover, a recently published review article from Saad et al. [24] thoroughly discussed the potential of ranolazine in prevention of not only atrial arrhythmias but also ventricular arrhythmias. Our findings will help in designing a randomized control trial to evaluate the efficacy, safety, dose regimen and cost-effectiveness analysis of ranolazine in AF management. Despite this promising finding, our study has several limitations. First, only four studies were included in the analysis, and the overall sample size was small. In addition, a minor difference was found in the study design among the included studies. Out of four studies, two studies were non-randomized retrospective studies. Moreover, the ranolazine dose was different in one study, and the duration of ranolazine therapy was different in each study. In the study by Miles et al. [15], a major limitation was the retrospective study design and comorbidities, such as heart failure, were more in the amiodarone group, which could have influenced the result. Moreover, it was the only study of the four wherein ranolazine was compared with amiodarone, as amiodarone was the standard therapy at that hospital. Hammond et al. study evaluated the patients by propensity matching, which could have reduced the bias, but it was also a retrospective design. The study by Tagarakis et al. was the first randomized trial comparing ranolazine to placebo in prevention of AF post cardiac surgery but the sample size was too small. In addition, low-dose ranolazine was used in that study compared with other studies. Last, the study by Bekheit et al. was a conference presentation; hence, we were unable to collect data in detail. Despite this minor discrepancy, the role of ranolazine in prevention of AF cannot be disregarded and it will help in designing future randomized clinical trials.