After the PALLAS trial, which was studying the effects of dronedarone (Multaq) in permanent atrial fibrillation (AF) patients, was halted by Sanofi-Aventis earlier this week, a further FDA review has shown that the drug increased death two-fold, and stroke and hospitalization three-fold.

As previously reported on this site, the PALLAS (Permanent Atrial fibrillation Outcome Study Using Dronedarone on Top of Standard Therapy) trial looked to assess the benefits of dronedarone (Multaq) in patients older than 65 years with permanent AF to reduce cardiovascular events or cardiovascular hospitalization of death from any cause.

“A critical question is whether and how the unfavorable results of the PALLAS study, obtained in patients with permanent atrial fibrillation, apply to patients who use Multaq for the approved indications (non-permanent atrial fibrillation, also known as paroxysmal or persistent atrial fibrillation),” the FDA wrote. Currently, the drug is approved for use in non-permanent AF patients. The decision was based on the results of the ATHENA trial.

Both the FDA and the European Medicines Agency (EMA) said that patients prescribed the drug should talk to their healthcare professionals about whether or not they should continue taking the drug. The agencies also urged healthcare professionals to stop prescribing the drug to permanent AF patients.

The drug was also caught under fire back in January when the FDA issued a Drug Safety Communication (DSC) reporting a rare but severe liver injury that was reported with the use of dronedarone.

While the PALLAS study results are considered preliminary at this time because they have not yet undergone quality assurance procedures, the FDA said that it will continue to evaluate how the preliminary results of the PALLAS study apply to patients taking the drug for paroxysmal or persistent AF or atrial flutter.

Made current as of June 30, the FDA reported that results of the PALLAS study showed that the rates of CV death, MI, stroke and systemic embolism were 2 percent in the study arm receiving the drug and 0.9 percent in the arm receiving placebo. The rates of death and unplanned CV hospitalization were reported to be 7.5 percent versus 5.1 percent. Additionally, the FDA reported that stroke occurred in 1.1 percent of the patients administered dronedarone compared to 0.4 percent of those who received placebo.

The EMA is conducting a review of the PALLAS study results, however, in the meantime the agency said, “Awaiting the finalization of the current review, prescribers in the European Union are reminded to follow the recommendations in the product information with respect to the indication, contraindications and warnings. Specifically, prescribers are advised to monitor patients regularly in order to ensure that they remain within the authorized indication and do not progress to permanent atrial fibrillation.”

EMA said that it expects to finalize its current review in September and will issue further advice at that time. Additionally, the FDA said that it will continue to review the preliminary results from the PALLAS study and will report final results when they are available.