ATLANTA--Patients with atrial fibrillation (AF) or atrial flutter (AFL) who transition to dronedarone (Multaq, Sanofi-Aventis) following prior treatment with amiodarone (Cordarone, Wyeth) were not associated with adverse events, according to a post-hoc analysis of pooled data from the EURIDIS and ADONIS trials presented Monday at the ACC.10 conference.
Lead researcher Peter Kowey, MD, chief of the division of cardiovascular diseases at the Main Line Health System in Wynnewood, Pa., told Cardiovascular Business News that the “most commonly used drug globally for atrial fibrillation is amiodarone, which is very effective but has a lot of toxicity that can affect multiple organs.” He also noted that its toxicity is accumulative, so the “longer a patient is on the drug, the better the chances of an adverse event.”
“The perception of dronedarone is that it's much safer, even though its less effective, so there are many patients that get switched,” Kowey said “The problem with this is that amiodarone tends to stick around in the body for awhile—it takes days to weeks to get it washed out of one’s system.” One concern is that too quick a switch would lead to added toxicity, he added.
In the large twin EURIDIS and ADONIS trials, there was no protocol for how to undergo this switch, so it was left up to the individual physician.
As a result, this analysis included 223 patients previously treated with amiodarone, in which dronedarone or placebo was initiated in a subgroup of 154 patients (Multaq 98; placebo 56) within two days of discontinuing amiodarone, and those who took longer than two days to switch.
The subgroup represents 18 percent of the patients enrolled in the EURIDIS and ADONIS studies (7.9 percent treated with dronedarone) and was compared with a group of patients who had no prior treatment with amiodarone (1,014). The researchers compared the groups on the primary study endpoint, time to first recurrence of AF/AFL as well as incidence of adverse events.
Kowey summarized that the “efficacy of the two arms was the same, and there did not appear to be any safety liability to an abrupt switch, based on this relatively small, retrospective study.”
The data “suggest it may be possible to initiate Multaq following discontinuation of amiodarone in paroxysmal and persistent patients within two days, while maintaining efficacy at preventing AF recurrence.”
However, he added that caution “should be given to heart rate and QTc intervals prior to consideration of early initiation of dronedarone.”
Yet, these results are “hypothesis generating,” according to Kowey, “and indicate that a prospective trial is warranted which is currently being put in place sponsored by the manufacturers.”