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The HARMONY Trial: Combined Ranolazine and Dronedarone in the Management of Paroxysmal Atrial Fibrillation: Mechanistic and Therapeutic Synergism.
The HARMONY Trial: Combined Ranolazine and Dronedarone in the Management of Paroxysmal Atrial Fibrillation: Mechanistic and Therapeutic Synergism.
- Source :
- Circulation: Arrhythmia & Electrophysiology; Oct2015, Vol. 8 Issue 5, p1048-1056, 9p
- Publication Year :
- 2015
-
Abstract
- <bold>Background: </bold>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. <bold>Methods and Results: </bold>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. <bold>Conclusions: </bold>HARMONY showed synergistic AFB reduction by moderate dose ranolazine plus reduced dose dronedarone, with good tolerance/safety, in the population enrolled. <bold>Clinical Trial Registration: </bold>ClinicalTrials.gov; Unique identifier: NCT01522651. [ABSTRACT FROM AUTHOR]
- Subjects :
- AMIODARONE
ATRIAL fibrillation
CARDIAC pacemakers
COMBINATION drug therapy
COMPARATIVE studies
DRUG synergism
RESEARCH methodology
MEDICAL cooperation
MYOCARDIAL depressants
RESEARCH
EVALUATION research
RANDOMIZED controlled trials
TREATMENT effectiveness
BLIND experiment
SODIUM channel blockers
THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 19413149
- Volume :
- 8
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- Circulation: Arrhythmia & Electrophysiology
- Publication Type :
- Academic Journal
- Accession number :
- 110484561
- Full Text :
- https://doi.org/10.1161/CIRCEP.115.002856