Dronedarone for A-Fib: A Non-Toxic Treatment Alternative?


Dronedarone (Multaq) is an antiarrhythmic drug which was developed for treating atrial fibrillation. In their search for a safe and effective drug for this condition, pharmaceutical companies have long imagined their holy grail: a drug that is as effective as amiodarone, but without its unique toxicity profile. Dronedarone was developed by Sanofi (the makers of amiodarone) specifically in the hope of creating that holy grail.


As antiarrhythmic drugs go, dronedarone is reasonably effective in treating atrial fibrillation. Unfortunately, this is not saying very much. Several clinical trials have demonstrated that dronedarone is moderately effective in maintaining a normal rhythm in people who have had atrial fibrillation.

Specifically, it has been shown to be significantly more effective than placebo. Still, 64 percent of patients treated with dronedarone had recurrent atrial fibrillation during the first year of treatment. (In contrast, 75 percent of patients who received placebo had recurrent atrial fibrillation.) This is roughly the rate of success seen with most other antiarrhythmic drugs—again, it’s not saying very much.

In a clinical trial comparing the effectiveness of dronedarone to amiodarone, dronedarone proved to be inferior to its “parent” drug.

Sixty-four percent of patients treated with dronedarone had recurrent atrial fibrillation at one year, compared to “only” 42 percent of those treated with amiodarone.

Side Effects 

Dronedarone is a derivative of amiodarone, which is the most effective, but most toxic, antiarrhythmic drug yet developed.

Unlike amiodarone, dronedarone does not contain iodine atoms. It is believed that the iodine in amiodarone produces some of the drug's striking toxic effects, especially the thyroid toxicity seen with the drug and perhaps the lung toxicity.

And as it turns out, dronedarone has not displayed the broad spectrum of unique toxicities associated with amiodarone. However, liver toxicity has been reported with dronedarone, and some cases of lung toxicity have also been seen.

Since its introduction, dronedarone has sent conflicting messages regarding its effect on overall mortality. Some studies have suggested that taking dronedarone increases cardiovascular mortality, while other studies seem to say it reduces mortality. While this conflicting evidence has never been fully resolved, it appears that the patients who may be at increased risk with dronedarone are older and have more serious underlying heart disease - especially heart failure - than patients who have done well with the drug.

The other side effects of dronedarone appear to be relatively benign. The most common reported side effects are diarrhea or nausea, slow heart rate and a rash.

The Bottom Line

Like all antiarrhythmic drugs, dronedarone should be used with caution.

Its recommended use is to help maintain a normal heart rhythm in patients who have had episodes of atrial fibrillation successfully stopped with cardioversion. If atrial fibrillation recurs while taking dronedarone, the drug should be stopped, and a different treatment strategy adopted.

The drug should be used with caution, if at all, in people over 65 years of age who have significant underlying cardiac disease, especially heart failure. It is best used in younger people who have only intermittent atrial fibrillation and who have otherwise healthy hearts.

So, at the end of the day, the dronedarone is not the holy grail.

Indeed, the story with this drug is the same story that has been heard many times with antiarrhythmic drugs—initial excitement, followed by disappointment. As a group, these drugs are only moderately effective, yet are among the most toxic drugs in medicine. They should be used only after careful consideration of all the alternatives, and when the potential benefits clearly outweigh the very real risks.


Hohnloser SH, Crijns HJGM, van Eickels M, et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med 2009; 360:668-678.

Singh BN, Connolly SJ, Crijns HJGM, et al. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med 2007; 357:987-99.

Connolly SJ, Camm AJ, Halperin JL, et al. Dronedarone in high-risk permanent atrial fibrillation. N Engl J Med 2011; DOI: 10.1056/NEJMoa1109867.

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