Dronedarone had no adverse effect on mortality in atrial fibrillation (AF) patients with congestive heart failure (CHF) and/or a left ventricular ejection fraction less than 0.35; and patients had a lower incidence of primary outcome events when allocated to dronedarone therapy, according to the ATHENA late-breaking clinical trial presented May 15 at the 30th annual meeting of the Heart Rhythm Society (HRS) in Boston.
Dronedarone (Multaq,Sanofi Aventis) is a multichannel blocking antiarrhythmic drug which has been shown to have rhythm- and rate-controlling effects in patients with AF. ATHENA is a randomized, placebo-controlled trial which showed that dronedarone reduces clinical outcomes including cardiovascular hospitalization, cardiovascular death or stroke in patients with AF or atrial flutter.
However, a previous study in CHF patients was stopped prematurely due to excess mortality in the dronedarone arm. Hence, lead investigator Stefan H. Hohnloser, MD, from J. W. Goethe University in Frankfurt, Germany, who presented the post-hoc study said that he and his colleagues analyzed data from ATHENA with respect to CHF and outcomes.
In the ATHENA trial, 2,327 patients received placebo and 2301 received dronedarone (400 mg bid). The researchers excluded patients in functional class IV CHF. Baseline and follow-up data regarding CHF and outcomes were carefully documented. The primary study endpoint was time to first cardiovascular hospitalization or death.
At randomization, 109 placebo patients and 91 dronedarone patients were in class III CHF. In those, the primary endpoint occurred in 71 placebo patients (eight deaths, 63 hospitalizations) compared to 40 patient in the dronedarone group (four deaths, 36 hospitalizations), according to the researchers.
During the study, Hohnloser reported that 21/109 placebo patients and 12/91 dronedarone patients died. Similar analyses were conducted in patients with a baseline left ventricular ejection fraction less than 0.35. Of 87 such patients in the placebo group, 47 had a primary outcome (including nine deaths) compared to 39/92 such dronedarone patients (five deaths).
Hohnloser and colleagues conducted a further analysis, examining patients who after randomization were noted to deteriorate into class IV CHF. This was observed in 54/2327 placebo patients and in 42/2301 dronedarone patients. When these patients were further followed, there was no significant difference in the incidence of the primary study outcome (33 in the placebo group, 27 in the dronedarone group).
"In patients with AF and stable CHF, dronedarone did not increase mortality and actually showed a trend towards reduction of cardiovascular hospitalizations and death," Hohnloser said