Ranolazine, dronedarone show synergistic effect on AF suppression
MedWire News: Results from experimental canine models suggest that the mild suppression of atrial fibrillation (AF) achieved with low-dose ranolazine or dronedarone is greatly augmented when both drugs are used in combination.
"Considering the relatively good safety profiles of both agents, our results suggest that the striking synergistic atrial-selective action of ranolazine and dronedarone may offer a unique combination therapy for AF that is both safe and effective," comment Charles Antzelevitch from Masonic Medical Research Laboratory in Utica, New York, USA, and team.
The researchers investigated the individual and combined in vitro effects of both drugs in ventricular, atrial, and pulmonary vein tissue samples of canine origin. Action potentials (APs) produced in response to dronedarone (10 µmol/l) and ranolazine (5 µmol/l) were measured using microelectrodes.
As reported in the Journal of the American College of Cardiology, Antzelevitch and colleagues found that when used separately, ranolazine and dronedarone failed to produce a notable change in the duration of APs generated in atrial or ventricular samples, although both drugs prolonged the atrial effective refractory period (ERP) and led to atrial post-repolarization refractoriness (PRR).
This effect was more marked with ranolazine than dronedarone.
Similarly, ranolazine inhibited the induction of AF more frequently than dronedarone, with a success rate of 29% versus 17%.
In combination, dronedarone and ranolazine appeared to act synergistically, producing a similar but more pronounced atrial-specific PRR. The success rate of AF inhibition was also greatly increased, more than three-fold, to 90% (9 out of 10 samples), when the drugs were combined.
In addition, persistent AF was terminated and AF reinduction was prevented at a rate of 60% (6 out of 10 samples) and 100% (6 out of 6 samples) when both drugs were used in combination.
The researchers highlight that ranolazine and dronedarone both inhibit sodium channels by differing mechanisms, meaning their synergistic action is to be expected.
They conclude: "The results of the present study provide validation of this concept as well as presenting further evidence in support of the hypothesis that a combination of predominantly open-state and inactivated-state blockers of the sodium channels... terminate and prevent the induction and reinduction of AF."
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By Lauretta Ihonor