Table 1.
Clinical Evidence for the Role of Ranolazine in AF
| Study | Design and aim | Methods | Results |
|---|---|---|---|
| Scirica et al25, 26 | A substudy of the MERLIN‐TIMI 36 randomized controlled trial | 6560 patients with NSTE‐ACS received ranolazine vs placebo in addition to the standard therapy. | Ranolazine showed a trend toward lower incidence of new‐onset AF at 7 d after randomization (RR: 0.74, 95% CI: 0.52‐1.05, P = 0.08). |
| Role of ranolazine in the prevention of arrhythmias in post–NSTE‐ACS patients | Holter ECG monitoring for the first 7 d after randomization | No increase in the incidence of pro‐arrhythmia | |
| At 1‐year follow‐up, ranolazine showed decrease in AF burden in the paroxysmal AF category (P = 0.015) as well as clinical AF‐related events compared with placebo (RR: 0.71, P = 0.01). | |||
| Tagarakis et al27 | Prospective, randomized, single‐blind, clinical trial | 102 patients received either ranolazine 375 mg bid for 3 d prior to surgery and until discharge, or usual care. | Ranolazine significantly lowered the incidence of POAF compared with the control group (8.8% vs 30.8%; P < 0.001). |
| Role of ranolazine in the prevention of POAF after on‐pump CABG surgery | Patients were monitored for the development of POAF. | ||
| Miles et al28 | Retrospective cohort study | 393 patients undergoing CABG received ranolazine 1500 mg preoperatively followed by 1000 mg bid for 10 to 14 d vs amiodarone 400 mg preoperatively followed by 200 mg bid for 10 to 14 d | Ranolazine significantly decreased the incidence of POAF compared with amiodarone (17.5% vs 26.5%; P = 0.035). |
| Ranolazine vs amiodarone for the prevention of POAF after CABG | |||
| Hammond et al29 | A single‐center, retrospective cohort study: | 205 patients received ranolazine 1000 mg preoperatively, then 1000 mg bid for 7 d or until discharge vs standard therapy only. | Ranolazine led to significant decrease in the incidence of POAF compared with control group (10.1% vs 41.9%; OR: 0.157, 95% CI: 0.067‐0.367, P < 0.0001). |
| Role of ranolazine in prevention of POAF after CABG, valvular, or combined surgeries | After propensity‐score matched‐pair analysis and conditional logistic regression, ranolazine was an independent predictor of preventing POAF (P < 0.0001). | ||
| Fragakis et al30 | Prospective randomized pilot study | 51 patients with recent‐onset (<48 h) AF eligible for pharmacologic cardioversion were randomized to a combined therapy of IV amiodarone plus single oral dose of ranolazine 1500 mg given at the time of randomization vs IV amiodarone alone. | Combined amiodarone/ranolazine therapy resulted in increased success of AF cardioversion (88% vs 65% in amiodarone‐only group; P = 0.056); and significant shortening of time to cardioversion (9.8 ± 4.1 vs 14.6 ± 5.3 h in amiodarone‐only group; P = 0.002). |
| Safety and efficacy of ranolazine plus amiodarone vs amiodarone alone for the conversion of recent‐onset AF | |||
| Simopoulos et al31 | Prospective, randomized, single‐blind, single‐site clinical trial | 41 patients were randomized to receive either ranolazine 375 mg bid orally plus IV amiodarone or IV amiodarone alone | Ranolazine shortened time to cardioversion of POAF when combined with amiodarone (19.9 ± 3.2 vs 37.2 ± 3.9 hours in amiodarone only group, P < 0.001). |
| Role of adding ranolazine to amiodarone in shortening time to conversion of POAF after CABG surgery | |||
| Murdock et al32 | Prospective cohort study | 18 patients with either new AF (n = 11) or paroxysmal AF (n = 7) received 2000 mg of ranolazine. 17 patients had underlying structural heart disease. | Ranolazine resulted in 72% conversion rate to SR within 6 h of administration. |
| Safety and efficacy of ranolazine as “pill in the pocket” therapy for cardioversion of new or paroxysmal AF | No pro‐arrhythmias or significant side effects reported. | ||
| Murdock et al33 | 3‐year retrospective analysis | 25 patients with persistent or permanent AF who failed either elective or emergent electric cardioversion and had been administered a single oral dose of 2000 mg ranolazine followed by another electric cardioversion attempt after 3.5 to 4 h | Ranolazine facilitated the restoration of SR in 19 of the 25 patients (76%). |
| Role of ranolazine in facilitating restoration of SR in patients with failed electric cardioversion. | 5 out of the 6 patients who were refractory to repeat electric cardioversion remained in permanent AF. | ||
| No adverse effects were reported. | |||
| Kowey et al34 (HARMONY trial) | Randomized, double‐blind, placebo‐controlled, parallel‐arm study | 134 patients with paroxysmal AF randomized into 5 groups to receive either ranolazine 750 mg bid alone, dronedarone 225 mg bid alone, ranolazine 750 mg bid plus dronedarone 225 mg bid, ranolazine 750 mg bid plus dronedarone 150 mg bid, or placebo. | The ranolazine 750 mg/dronedarone 150 mg combination decreased AF burden by 45% compared with placebo (P = 0.072). |
| Role of combination of ranolazine and dronedarone in reducing the burden of AF in patients with paroxysmal AF | 12‐wk follow‐up of the AF burden | The ranolazine 750 mg/dronedarone 225 mg combination decreased AF burden by 59% compared with placebo (P = 0.008). | |
| Neither ranolazine nor dronedarone alone significantly reduced the AF burden | |||
| De Ferrari et al35 (RAFFAELLO trial) | Prospective, multicenter, randomized, double‐blind, placebo‐control, parallel‐group phase 2 dose‐ranging trial | 241 patients with persistent AF were randomized to either placebo or ranolazine, with doses ranging from 375 to 750 mg bid, 2 h after successful electrical cardioversion. | AF recurred in 56.4%, 56.9%, 41.7%, and 39.7% in the placebo group, ranolazine 375‐mg group, ranolazine 500‐mg group, and ranolazine 750‐mg group, respectively. |
| Safety and efficacy of ranolazine in the prevention of AF recurrence after successful electrical cardioversion | No dose of ranolazine significantly prolonged time to AF recurrence; however, reduction in overall AF recurrence in combined 500‐mg and 750‐mg groups showed borderline significance compared with placebo (P = 0.053) and was significant compared with the 375‐mg group (P = 0.035). |
Abbreviations: AF, atrial fibrillation; bid, twice daily; CABG, coronary artery bypass grafting; CI, confidence interval; ECG, electrocardiogram; HARMONY, A Study to Evaluate the Effect of Ranolazine and Dronedarone When Given Alone and in Combination in Patients With Paroxysmal Atrial Fibrillation; IV, intravenous; MERLIN‐TIMI 36, Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST‐Segment Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36; NSTE‐ACS, non–ST‐segment elevation acute coronary syndrome; OR, odds ratio; POAF, postoperative atrial fibrillation; RAFFAELLO, Ranolazine in Atrial Fibrillation Following an Electrical Cardioversion; RR, risk reduction; SR, sinus rhythm.