FDA’s committee recommends approval of dronedarone for AF


The FDA’s Cardiovascular and Renal Drugs Advisory Committee recommended on the 18 March, 2009 the approval of the dronedarone 400mg oral tablets (Multaq, Sanofi-Aventis) for the treatment of patients with atrial fibrillation or atrial flutter, for the reduction of the risk of cardiovascular hospitalisation or death. The committee voted 10 to 3 in favour of the approval of dronedarone.

The efficacy of the new drug was assessed in the ATHENA trial. The results of the study were published in the 12 February 2009 issue of the New England Journal of Medicine.

Data from the ATHENA, a multi-centre trial involving 4,628 patients with moderated to high-risk paroxysmal or persistent atrial fibrillation, have shown 24% reduction in all-cause mortality and cardiovascular hospitalisations (primary endpoint), as well as a 29% reduction in risk of cardiovascular death on top of standard therapy and a 45% reduction in the risk of arrhythmic death. Study investigators believe no other antiarrhythmic therapy has achieved such reductions. Importantly, the reduction was achieved in patients who were in most cases receiving appropriate antithrombotic therapy. Both arms showed a similar rate of adverse effects.

Dronedarone is intended to be an alternative to amiodarone (Cordarone), the treatment of choice for older patients with atrial fibrillation who have structural heart disease.

The primary efficacy parameter was the combined endpoint of time to first cardiovascular hospitalisation and death from any cause. Secondary efficacy parameters were death of any cause, death from cardiovascular causes, and cardiovascular hospitalisation.

The inclusion criteria was patients aged 75 years or older, or patients aged at least 70 years with one or more of the following risk factors at baseline: hypertension (taking antihypertensive drugs of at least two different classes), diabetes, prior cerebrovascular accident (stroke or transient ischaemic attack) or systemic embolism, left atrium diameter greater than or equal to 50mm by echocardiography, left ventricular ejection fraction less than 0.40 by 2D-echocardiography. Inclusion criteria also included availability of one electrocardiogram within the previous six months, showing that the patient was or is in atrial fibrillation/atrial flutter and availability of one electrocardiogram within the previous six months, showing that the patient was or is in sinus rhythm.

Mean follow-up period was 21+5 months. The primary outcome occurred in 734 patients (31.9%) in the dronedarone group and in 917 patients (39.4%) in the placebo group. There were 116 deaths (5%) in the dronedarone group and 139 (6%) in the placebo group, and 63 deaths from cardiovascular causes (2.7%) in the dronedarone group and 90 (3.9%) in the placebo group, largely due to a reduction in the rate of death from arrhythmia with dronedarone.