How will the son of amiodarone — dronedarone — fit into the family of antiarrhythmic drugs?

Dear Readers, Amiodarone is arguably the most effective antiarrhythmic available. Although it has only been approved for use by the FDA to treat life-threatening ventricular arrhythmias, it is commonly used off-label for atrial fibrillation (AF). In clinical trials, amiodarone has been shown to be about twice as effective in the prevention of recurrent AF as sotalol and propafenone, and is considered appropriate therapy for many patients with AF based on the 2006 ACC/AHA/ESC Guidelines. However, its limitations are legendary. Amiodarone can cause organ toxicity, most commonly affecting the thyroid, liver, lungs, and eyes. The toxicity of amiodarone is considered such a problem, that in 2005 the FDA issued a notice that a medication guide must be dispensed with every prescription for amiodarone. Drug interactions with amiodarone pose an additional risk. Concerns related to the use of amiodarone are well founded. However, the risks have become so notorious that it is often difficult to prescribe even when it might be appropriate. Many patients seen by a physician for AF have already ruled out the possibility of ever taking amiodarone based on what they have already heard from their family, friends, and other physicians. “Find an amiodarone lawyer near you” links are now common on the Internet. In April 2003, the Chicago Tribune ran an article about a $10 million settlement by the manufacturer of amiodarone after a man alleged that he became blind from optic neuritis caused by amiodarone. The plaintiff’s attorney assured that confidentiality would not be part of the settlement. Although amiodarone may indeed cause optic neuritis, this story created havoc with hundreds of patients calling their physicians the next day asking whether or not they should stop their drug. Much of amiodarone’s toxicity can be attributed to the large amount of iodine it contains. In an effort to develop an amiodarone-like anti-arrhythmic drug without the same toxicity, Sanofi-aventis has developed a non-iodinated form called dronedarone (brand name, Multaq®). In two randomized placebo controlled trials, dronedarone was found to be more effective than placebo in maintaining sinus rhythm. The results of the ATHENA trial of dronedarone, the largest randomized trial involving any antiarrhythmic drug, were presented in May 2008 at the Heart Rhythm Society meeting, and the final results were published in the February 12, 2009 issue of the New England Journal of Medicine. The ATHENA trial randomized over 4,500 elderly patients with AF in 37 countries to dronedarone (400 mg twice daily) or placebo. The trial enrolled patients ≥75 years old or ≥70 if they had at least one cardiovascular risk factor, such as hypertension, diabetes, prior stroke, or transient ischemic attack, an enlarged left atrium, or an LVEF Disclosures: Dr. Knight was an investigator for the ATHENA trial and is on the Data and Safety Monitoring Board for the DIONYSOS trial. Sincerely, Bradley P. Knight, MD, FACC, FHRS Editor-in-Chief, EP Lab Digest