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Ranolazine and dronedarone in AF management: the HARMONY trial

Moderate dose ranolazine plus reduced dose dronedarone produces synergistic atrial fibrillation burden (AFB) reduction, with good tolerance/safety, according to results from the HARMONY trial published recently in Circulation: Arrhythmia and Electrophysiology.1

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. The authors hypothesised that combining agents with multiple anti-AF mechanisms at reduced individual drug doses might produce synergistic efficacy plus better tolerance/safety.

HARMONY tested midrange ranolazine (750 mg BID) combined with two reduced dronedarone doses (150 mg BID and 225 mg BID; chosen to reduce dronedarone’s negative inotropic effect) over 12 weeks in 134 patients with paroxysmal AF and implanted pacemakers where AF burden (AFB) could be continuously assessed.

Patients were randomised 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.


1. Reiffel JA, Camm AJ, Belardinelli L, et al. Circ Arrhythm Electrophysiol 2015;8:1048–56.

Published on: October 30, 2015

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  • ArrhythmiaAlliance
  • Stars
  • Anticoagulation Europe
  • Atrial Fibrillation Association

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