Effect of ranolazine on atrial fibrillation in patients with non-ST elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 trial

Abstract

NCT00099788.

The Significance of the Late Na+ Current for Arrhythmia Induction and the Therapeutic Antiarrhythmic Potential of Ranolazine

“…Recently, evidence from clinical trials has highlighted the potential antiarrhythmic efficacy of ranolazine, a sodium channel blocker with rapid unbinding kinetics. [2][3][4][5] Furthermore, ranolazine displays a favorable safety profile even in patients with structural heart disease and has already been approved for the treatment of chronic angina. 6,7 This review focuses on the role of the late sodium current, I Na,late , in arrhythmogenesis and the current evidence suggesting a potential antiarrhythmic role for ranolazine and its mechanisms of action.…”

“…3 Moreover, patients treated with ranolazine showed a tendency toward reduced new-onset AF (P ¼ .08), although the incidence of AF was relatively low in this trial. 4 All sodium channel blockers are able to inhibit both I Na,late and I Na,peak . There is evidence that in the failing ventricle, inhibition of I Na,peak by ranolazine is much less potent than that of I Na,late , with IC 50 values of 6.5 mmol/L (I Na,late ) and 244 mmol/L (I Na,peak ), 114 although this remains controversial as some reports show inhibition of I Na,peak also in the ventricle by ranolazine.…”

“…38 Furthermore, the anti-AF potential of ranolazine has been shown in animal 116 and human [2][3][4]117 studies. Of note, the human study by Miles et al was conducted postoperatively and therefore concerns a form of AF with alternative characteristics, which could be considered a study limitation.…”

Ranolazine in Cardiac Arrhythmia

“…25 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). 26 …”

“…The authors of this study considered high-dose ranolazine a novel ''pill in the pocket'' medication for conversion of AF in patients with structural heart disease. 32 In a case series of 25 patients who failed attempts of electric cardioversion of AF, a single oral 25,26 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.…”