Meeting News Coverage

HARMONY: Ranolazine, dronedarone combination reduced AF burden

SAN FRANCISCO — A combination of ranolazine and dronedarone reduced atrial fibrillation burden better than either alone in patients with paroxysmal atrial fibrillation, according to findings from the phase 2 HARMONY trial.

These are “convincing data regarding the potential of this combination to have a favorable effect on the medical treatment of AF, a condition for which new treatments are sorely needed,” Peter R. Kowey, MD, FHRS, from Lankenau Medical Center and Institute for Medical Research, Wynnewood, Pa., told Cardiology Today.

The researchers hypothesized that a combination of ranolazine (Ranexa, Gilead Sciences), an antianginal drug, and low-dose dronedarone (Multaq, Sanofi Aventis), an anti-AF drug, would be effective for suppressing AF due to multichannel ion effects. Both drugs have demonstrated modest effects against AF, but dronedarone at conventional doses has a signal for harm, Kowey said in a presentation at the Heart Rhythm Society Annual Scientific Sessions.

The HARMONY trial included 134 patients with paroxysmal AF and dual-chamber pacemakers with the ability to detect AF and record and store electrograms who were randomly assigned to one of five groups: placebo; ranolazine 750 mg twice daily; dronedarone 225 mg twice daily; ranolazine 750 mg and dronedarone 225 mg twice daily; or ranolazine 750 mg and dronedarone 150 mg twice daily.

Reduced AF burden

The primary endpoint was relative and absolute change from baseline in AF burden at 12 weeks.

Compared with placebo, the group receiving ranolazine 750 mg and dronedarone 225 mg had a greater percentage change in AF burden from baseline to 12 weeks (P=.008), according to Kowey, the Cardiology Today Arrhythmia Disorders Section Editor.

Compared with placebo, the group receiving ranolazine 750 mg and dronedarone 150 mg (P=.072) and the group receiving ranolazine 750 mg only (P=.49) had a non-significant reduction in AF burden. The group receiving dronedarone 225 mg alone had no difference in percentage change in AF burden compared with the placebo group and had a slight increase in AF burden (P=.78), he said.

The percentages of patients with a ≥70% reduction of AF burden between baseline and 12 weeks were as follows: ranolazine 750 mg and dronedarone 225 mg group, 45%; ranolazine 750 mg and dronedarone 150 mg group, 27%; ranolazine 750 mg group, 17%; dronedarone 225 mg group, 9%; and placebo group, 11%, according to Kowey.

Few serious adverse events

Three serious adverse events were determined to be related to the study drug, one in the ranolazine 750 mg group, one in the dronedarone 225 mg group and one in the ranolazine 750 mg and dronedarone 225 mg group, Kowey said. He added that there were no deaths during the study, and the rates of discontinuation of the study drug were similar across all five groups.

“There is much to do to prove safety and effectiveness in an appropriately ill patient population, so the phase 3 experience will be pivotal in determining the impact of this new and fascinating approach on clinical practice,” Kowey said in an interview. – by Erik Swain

For more information:

Kowey PR. Abstract LB03-05. Presented at: Heart Rhythm Society Annual Scientific Sessions; May 7-10, 2014; San Francisco.

Disclosure: The study was funded by Gilead Sciences. Kowey reports consulting for Gilead Sciences and Sanofi Aventis.

SAN FRANCISCO — A combination of ranolazine and dronedarone reduced atrial fibrillation burden better than either alone in patients with paroxysmal atrial fibrillation, according to findings from the phase 2 HARMONY trial.

These are “convincing data regarding the potential of this combination to have a favorable effect on the medical treatment of AF, a condition for which new treatments are sorely needed,” Peter R. Kowey, MD, FHRS, from Lankenau Medical Center and Institute for Medical Research, Wynnewood, Pa., told Cardiology Today.

The researchers hypothesized that a combination of ranolazine (Ranexa, Gilead Sciences), an antianginal drug, and low-dose dronedarone (Multaq, Sanofi Aventis), an anti-AF drug, would be effective for suppressing AF due to multichannel ion effects. Both drugs have demonstrated modest effects against AF, but dronedarone at conventional doses has a signal for harm, Kowey said in a presentation at the Heart Rhythm Society Annual Scientific Sessions.

The HARMONY trial included 134 patients with paroxysmal AF and dual-chamber pacemakers with the ability to detect AF and record and store electrograms who were randomly assigned to one of five groups: placebo; ranolazine 750 mg twice daily; dronedarone 225 mg twice daily; ranolazine 750 mg and dronedarone 225 mg twice daily; or ranolazine 750 mg and dronedarone 150 mg twice daily.

Reduced AF burden

The primary endpoint was relative and absolute change from baseline in AF burden at 12 weeks.

Compared with placebo, the group receiving ranolazine 750 mg and dronedarone 225 mg had a greater percentage change in AF burden from baseline to 12 weeks (P=.008), according to Kowey, the Cardiology Today Arrhythmia Disorders Section Editor.

Compared with placebo, the group receiving ranolazine 750 mg and dronedarone 150 mg (P=.072) and the group receiving ranolazine 750 mg only (P=.49) had a non-significant reduction in AF burden. The group receiving dronedarone 225 mg alone had no difference in percentage change in AF burden compared with the placebo group and had a slight increase in AF burden (P=.78), he said.

The percentages of patients with a ≥70% reduction of AF burden between baseline and 12 weeks were as follows: ranolazine 750 mg and dronedarone 225 mg group, 45%; ranolazine 750 mg and dronedarone 150 mg group, 27%; ranolazine 750 mg group, 17%; dronedarone 225 mg group, 9%; and placebo group, 11%, according to Kowey.

Few serious adverse events

Three serious adverse events were determined to be related to the study drug, one in the ranolazine 750 mg group, one in the dronedarone 225 mg group and one in the ranolazine 750 mg and dronedarone 225 mg group, Kowey said. He added that there were no deaths during the study, and the rates of discontinuation of the study drug were similar across all five groups.

“There is much to do to prove safety and effectiveness in an appropriately ill patient population, so the phase 3 experience will be pivotal in determining the impact of this new and fascinating approach on clinical practice,” Kowey said in an interview. – by Erik Swain

For more information:

Kowey PR. Abstract LB03-05. Presented at: Heart Rhythm Society Annual Scientific Sessions; May 7-10, 2014; San Francisco.

Disclosure: The study was funded by Gilead Sciences. Kowey reports consulting for Gilead Sciences and Sanofi Aventis.

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