In a commentary, published April 23 in the Journal of the American College of Cardiology, of the anti-arrhythmic drug dronedarone (Multaq, Sanofi-Aventis), researchers concluded that the controversial drug is only modestly effective and has no clear safety benefits.
The researchers from Cedars-Sinai Heart Institute in Los Angeles assessed data on dronedarone submitted during the drug's FDA approval process and determined that dronedarone is 50 percent less effective than amiodarone (Cordarone, Wyeth/Pfizer). Despite initial hopes that dronedarone would cause fewer side effects than amiodarone, the studies submitted to the FDA do not confirm that, the researchers concluded.
"We believe that dronedarone should only be used as a second-line or third-line agent in individuals that are not able to tolerate amiodarone or other first-line agents recommended by the guidelines," according to senior author Sanjay Kaul, MD, director of the Vascular Physiology and Thrombosis Research Lab at Cedars-Sinai.
According to the authors, dronedarone received widespread attention recently due to a controversial lecture sponsored by Sanofi-Aventis that touted its off-label use. When the drug received a green light from the FDA in 2009, its approval was for reducing the risk of cardiovascular hospitalization in patients with nonpermanent atrial fibrillation or atrial flutter, rather than as a drug indicated for suppression of arrhythmia, says Kaul.
"Dronedarone has, at best, modest effectiveness as an anti-arrhythmic agent, and it has not been proven to be any safer than amiodarone," says Kaul. "Amiodarone does have the potential for toxicity that can adversely impact quality of life, but it's also very effective and we can manage side effects or avoid them by lowering the dose. The argument that dronedarone is potentially safer than amiodarone is weakened by the fact that it's also half as effective. However, patient preference is an important consideration in treatment decisions. There are some patients who might consider improved short-term tolerability over reduced efficacy an acceptable tradeoff."
Based on the current studies, according to Kaul, physicians should be very cautious about using dronedarone for off-label indications such as ventricular arrhythmia, and should avoid using it in high-risk patients such as those with advanced heart failure or those with recently decompensated heart failure requiring hospitalization or special attention.
"Dronedarone has very modest efficacy as an anti-arrhythmic agent, and based on the current evidence its use for the treatment of nonpermanent atrial fibrillation or atrial flutter can only be supported as a second- or third-line agent after guideline-recommended first-line agents have failed," said Kaul.