Combining ranolazine 750 mg BID and dronedarone 225 mg BID reduced atrial fibrillation burden by 59% versus placebo (P=0.008) in patients with paroxysmal AF and pacemakers.
RCT (n=134)
Double-blind
Randomized
Does the combination of ranolazine and dronedarone reduce atrial fibrillation burden in patients with paroxysmal AF and implanted pacemakers?
The combination of moderate-dose ranolazine and reduced-dose dronedarone synergistically reduces atrial fibrillation burden in patients with paroxysmal AF.
Effect estimate: 59% reduction
p-value: p=0.008
BACKGROUND: Atrial fibrillation (AF) requires arrhythmogenic changes in atrial ion channels/receptors and usually altered atrial structure. AF is commonly treated with antiarrhythmic drugs; the most effective block many ion channels/receptors. Modest efficacy, intolerance, and safety concerns limit current antiarrhythmic drugs. We hypothesized that combining agents with multiple anti-AF mechanisms at reduced individual drug doses might produce synergistic efficacy plus better tolerance/safety. METHODS AND RESULTS: HARMONY tested midrange ranolazine (750 mg BID) combined with 2 reduced dronedarone doses (150 mg BID and 225 mg BID; chosen to reduce dronedarone's negative inotropic effect-see text below) over 12 weeks in 134 patients with paroxysmal AF and implanted pacemakers where AF burden (AFB) could be continuously assessed. Patients were randomized double-blind to placebo, ranolazine alone (750 mg BID), dronedarone alone (225 mg BID), or one of the combinations. Neither placebo nor either drugs alone significantly reduced AFB. Conversely, ranolazine 750 mg BID/dronedarone 225 mg BID reduced AFB by 59% versus placebo (P=0.008), whereas ranolazine 750 mg BID/dronedarone 150 mg BID reduced AFB by 43% (P=0.072). Both combinations were well tolerated. CONCLUSIONS: HARMONY showed synergistic AFB reduction by moderate dose ranolazine plus reduced dose dronedarone, with good tolerance/safety, in the population enrolled. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; Unique identifier: NCT01522651.
Reiffel et al. (Fri,) conducted a rct in Paroxysmal atrial fibrillation (n=134). Ranolazine combined with dronedarone vs. Placebo, ranolazine alone (750 mg BID), or dronedarone alone (225 mg BID) was evaluated on Atrial fibrillation burden (AFB) (59% reduction, p=0.008). Combining ranolazine 750 mg BID and dronedarone 225 mg BID reduced atrial fibrillation burden by 59% versus placebo (P=0.008) in patients with paroxysmal AF and pacemakers.