DURHAM, NORTH CAROLINA. Amiodarone (Cordarone) is the most effective antiarrhythmic drug on the market today, although a recent trial found that its efficacy in keeping atrial fibrillation patients afib-free for a year is only 34%. Apart from questionable efficacy, amiodarone also has a long list of potentially very serious side effects including thyrotoxicosis, hypothyroidism, pulmonary toxicity (fatal in 10% of cases), liver toxicity, optic neuropathy (including loss of vision), and blurred vision.
The amiodarone molecule contains 37.5% by weight of iodine and it is widely believed that it is the iodine that causes most of the adverse effects of the drug. Thus, it is not surprising that much research has been devoted to finding a drug similar to amiodarone (a benzofuran derivative), but without the iodine component. This search has now resulted in the development of dronedarone (Multaq). Dronedarone has undergone several large-scale clinical trials, which, with the exception of one (ANDROMEDA) involving patients with severe congestive heart failure, have found it to be safe and with no significant adverse effects after one year of use. However, an increase in serum creatinine level (an indicator of possible kidney toxicity) has been observed in some trials, as have gastrointestinal problems like diarrhea, nausea and vomiting.
Two large-scale clinical trials (EURIDIS and ADONIS) evaluated the effect of 400 mg of dronedarone in 1237 AF patients. At the end of the trial (12 months from the start), 24.8% of the placebo group were still in normal sinus rhythm as compared to 35.9% in the dronedarone group.
A group of researchers from Duke University Medical Center has now performed a comparison of amiodarone and dronedarone to establish their relative efficacy and safety. Unfortunately, their study does not involve a head-to-head comparison between the two drugs in which half of the study group is randomized to one drug, while the other half receives the other drug. Rather, the researchers selected 4 trials comparing amiodarone to placebo and 4 comparing dronedarone to placebo. Also included was one small trial of amiodarone vs. dronedarone. Unfortunately, the study population was quite heterogeneous in that the 4 dronedarone/placebo studies excluded patients with permanent AF, while 2 of the 4 amiodarone studies excluded patients with paroxysmal afib. None of the studies included patients with highly symptomatic afib and none paid any attention to quality-of-life factors or to the incidence of stroke and bleeding.
Nevertheless, the researchers, not unexpectedly, found amiodarone to be about twice as effective as dronedarone in maintaining sinus rhythm. On the other hand, more patients discontinued amiodarone than gave up on dronedarone and there was a trend towards overall greater mortality in the amiodarone group. In interpreting this finding, it should be kept in mind that members of the amiodarone group tended to be in worse shape health-wise than those in the dronedarone group.
The researchers conclude that for every 1,000 patients treated with dronedarone (800 mg/day @ a cost of $9.00/day) rather than with amiodarone (200 mg/day @ a cost of $3.50/day), there would be 228 more recurrences of afib at one year, offset by 9.6 fewer deaths and 63 fewer adverse events requiring discontinuation of drug therapy.
Piccini, JP, et al. Comparative efficacy of dronedarone and amiodarone for the maintenance of sinus rhythm in patients with atrial fibrillation. Journal of the American College of Cardiology, Vol. 54, No. 12, September 15, 2009, pp. 1089-95
Chan, PS, et al. Amiodarone or dronedarone for atrial fibrillation: too early to know the winner? Journal of the American College of Cardiology, Vol. 54, No. 12, September 15, 2009, pp. 1096-98
Editor's comment: Due to the obvious lack of attention paid to ensuring that the groups of patients compared were indeed comparable, i.e. paroxysmal afibbers compared with paroxysmal afibbers, and permanent afibbers compared with other permanent afibbers, I am not really certain that one can draw any hard and fast conclusions from this study other than perhaps that dronedarone is likely less effective, but safer than amiodarone.