Archief Roodbont

Dronedarone reduces CV mortality in atrial fibrillation

12 February 2009

MedWire News: The antiarrhythmic drug dronedarone reduces the risk for cardiovascular hospitalization and death in patients with atrial fibrillation (AF), a large clinical trial has shown.

The ATHENA study was a placebo-controlled, double-blind study that assessed the efficacy of dronedarone in patients with high-risk AF or atrial flutter (Afl). Dronedarone is a benzofuran derivative with a pharmacologic profile similar to that of amiodarone but different relative effects on individual ion channels.

The study enrolled 4628 patients at 550 sites in 37 countries; all had AF/Afl and additional risk factors for death. They were randomized to take dronedarone 400 mg twice daily or placebo and followed-up for a mean duration of 21 months.

The study drug was discontinued prematurely in 30.2% and 30.8% of the dronedarone and placebo groups, respectively, mostly because of adverse events.

The primary outcome – a composite of hospitalization for cardiovascular events or death – occurred in 31.9% of the dronedarone group versus 39.4% of the placebo group, a statistically significant difference (hazard ratio[HR]=0.76, p<0.001).

The main effect of dronedarone was to reduce cardiovascular deaths (HR=0.71, p=0.03), mainly from arrhythmia, whereas the rate of death from any cause was not significantly different between the groups (HR=0.84, p=0.18).

Dronedarone was associated with a significantly higher frequency of adverse events versus placebo; common side effects included bradycardia, QT-interval prolongation, diarrhea, nausea, rash, and an increase in serum creatinine.

Rates of thyroid or pulmonary disorders did not differ between the treatment groups, although the trial investigators remark that the duration of follow-up may have been too short for these effects to emerge.

Furthermore, the very high rate of study-drug discontinuation may have resulted in an underestimate of the benefit of dronedarone, say the investigators, but may also have limited the likelihood of demonstrating an increase in the rate of adverse events.

ATHENA is the first trial of an antiarrhythmic drug to assess the effect of treatment on morbidity/mortality. “Therefore, it is not possible to know the relative efficacy or safety of dronedarone as compared with other drugs for this outcome,” write Stefan Hohnloser (JW Goethe University, Frankfurt, Germany) and co-authors in the New England Journal of Medicine.

“The efficacy and tolerability of dronedarone and amiodarone as used to prevent the recurrence of AF are currently being investigated in an ongoing randomized trial.”

MedWire is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

N Engl J Med 2009; 360: 668–678