To add to the recent saga surrounding dronedarone (Multaq), results of an analysis of the ATHENA trial offered a dose of good news after researchers in Denmark found that the drug reduced the risk for cardiovascular hospitalization and total hospitalizations. The post-hoc data analysis was published in the August issue of Europace.
The anti-arrhythmic dronedarone has been under fire in recent months after the drug was shown to be associated with severe liver injury and increased cardiovascular events. Last month, the drug's developer, Sanofi-Aventis, halted the PALLAS trial, which was studying the effects of dronedarone in permanent atrial fibrillation patients after the drug was found to increase the risk of CV events. The FDA review reported that dronedarone increased death two-fold, and stroke and hospitalization three-fold; however, the drug’s current indications are for use in non-permanent atrial fibrillation (AF) patients.
ATHENA [A placebo-controlled, double-blind, parallel-arm Trial to assess the efficacy of dronedarone 400 mg twice a day (bid) for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter] was a randomized, double-blind, placebo-controlled trial conducted at 551 centers in 37 countries; and 4,628 patients with paroxysmal/persistent AF were recruited to take part in the study between June 29, 2005, and Dec. 30, 2006. Patients were followed up for a minimum of one year.
ATHENA results showed that dronedarone significantly reduced the number of first CV hospitalizations compared to placebo and showed that the drug increased the time to first hospitalization for CV events. The current analysis set out to evaluate the effect of dronedarone on hospitalizations by examining all hospitalization events and hospital length of stay in patients with paroxysmal or persistent AF or atrial flutter.
Patients were assigned at random to receive a 400 mg dose of dronedarone (2,301 patients) or placebo (2,327 patients). An unplanned hospitalization was categorized as either CV or non-CV related. Patients had a mean age of 71.6 years and 53 percent were male.
The analysis, conducted by Christian Torp-Pedersen of the Gentofte Hospital in Hellerup, Denmark, and colleagues, showed that the number of first CV hospitalizations was decreased in the patients who received dronedarone compared with those who received placebo; 675 patients in the dronedarone group vs. 859 in the placebo group.
Torp-Pedersen and colleagues reported that dronedarone significantly reduced the risk of a first CV hospitalization and that the risk of first non-CV hospitalization was similar in both groups. Nearly half of the CV hospitalizations were AF-related, with a median hospital stay of four nights.
Of the first CV hospitalizations, those that were related to AF and acute coronary syndromes (ACS) were fewer in the dronedarone arm compared with the placebo arm; 335 vs. 510 for AF and 62 vs. 89 for ACS. Additionally, the researchers reported that the number of hospitalizations for stroke or transient ischemic attack (TIA) was not significantly reduced; 43 in the dronedarone group vs. 61 in the placebo group. Heart failure hospitalizations occurred in 112 patients in the dronedarone arm and 132 patients in the placebo arm.
Lastly, there was no significant difference between the number of first non-CV hospitalizations between groups; 516 in the dronedarone arm and 533 patients in the placebo arm.
Nearly a quarter of the patients in each group had at least one hospitalization due to any cause. Multiple CV hospitalizations were reported in 12.3 percent of patients in the dronedarone group and 15.9 percent of patients in the placebo group.
“The main finding of this ATHENA post-hoc analysis is that dronedarone reduces the number of CV hospitalizations and reduces the length of hospital stay for CV reasons,” the authors wrote. “It is also noteworthy that hospitalizations related to acute coronary syndromes were reduced.
“While hospitalizations related to acute coronary syndromes could be reduced by less frequent AF, one might speculate that the heart-rate-lowering effect of dronedarone may be important. Dronedarone slows the heart rate not only during AF but also during sinus rhythm,” the authors noted.
“In conclusion, treatment of patients with paroxysmal or persistent AF or AFL with dronedarone is associated with a marked reduction in the number and duration of CV hospitalizations,