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Adverse effects of dronedarone

LEIPZIG, GERMANY. A new study supports the contention that the antiarrhythmic drug dronedarone (Multaq) is largely ineffective and associated with a high incidence of adverse events. Dronedarone is a benzofuran derivative similar to amiodarone but without the iodine component. Initial trials showed it to be substantially less effective than amiodarone, but having fewer serious side effects. Later studies indicated that the drug is associated with an increased risk of liver and kidney damage.

The German study was carried out at Leipzig Heart Centre and involved 91 patients with atrial fibrillation (AF) and 29 patients with atypical (non-isthmus-dependent) atrial flutter (AFL). Of the 91 patients with AF, 30 had paroxysmal AF, while 61 had persistent AF. The average age of the study participants was 67 years, 53% were women, 67% had mild to moderate heart failure (New York Heart Association Class II or III), 93% had hypertension, 24% were diabetic, and 28% had undergone a previous catheter ablation.

The patients with persistent AF underwent cardioversion after a 3 to 5 day pre-treatment with 400 mg of dronedarone twice daily. All patients were then followed up at 4 weeks and 6 to 9 months after initiation of dronedarone therapy (400 mg twice daily). Follow-up visits included 12-lead electrocardiography, 7-day Holter monitoring, and assessment of liver and kidney function. Recurrence of AF and AFL was defined as atrial arrhythmia lasting 30 seconds or longer.

After the initial 3 to 5 day drug treatment phase, 6% of patients discontinued the drug after a failed cardioversion and 10% discontinued it after experiencing an adverse event. Discontinuation rates at 4 weeks were 23% because of inefficacy and 14% because of adverse events. Corresponding discontinuation rates at the 6 to 9 months check-up were 13% and 9%. Overall, only 27% of the original study group were still taking dronedarone at the last check-up. Discontinuation was due to inefficacy in 42% of patients and due to adverse events in 32%. The most common adverse event was bradycardia or atrioventricular block followed by gastrointestinal problems and QT-interval prolongation. One patient experienced acute renal failure after 6 weeks of dronedarone therapy.

At the 4 week check-up only 33% of patients were in sinus rhythm and this percentage declined to 20% at the 6 to 9 months check-up. Sinus rhythm maintenance was not significantly greater in patients who had undergone one ablation or therapy with Class I (flecainide and propafenone) or Class III (amiodarone, sotalol or dofetilide) antiarrhythmics. Reversal from persistent to paroxysmal AF was observed in 23 patients, while progression from paroxysmal to persistent AF occurred in 6 patients. Ten patients converted from AF to AFL as compared to only 2 patients who converted from AFL to AF.

The researchers conclude that dronedarone is associated with frequent adverse events and moderate antiarrhythmic efficacy requiring discontinuation in most patients (73% of the study group) within the first 9 months of use.
Lobe, S, et al. Usefulness of dronedarone in patients with atrial arrhythmias. American Journal of Cardiology, Vol. 111, 2013, pp. 1311-14

Editor’s comment: Several electrophysiologists have previously expressed their misgivings about the drug. Dr. Steven Nissen of the Cleveland Clinic believes dronedarone is outright dangerous and Dr. Sanjay Kaul of Cedar-Sinai Medical Center in Los Angeles says that the drug does not even appear to be safe in intermediate-risk patients. I think dronedarone deserves a place, alongside digoxin and sotalol, as the most useless pharmaceutical drug for AF patients.

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