Patients receiving dronedarone for atrial fibrillation on top of adequate antithrombotic medication presented a significantly lower incidence of stroke, according to Stefan Hohnloser, JW Goethe University, Frankfurt, Germany.
Hohnloser presented sub-analyses of the ATHENA trial (A placebo-controlled, double-blind, parallel-arm trial to assess the efficacy of dronedarone 400 mg BID for the prevention of cardiovascular hospitalization or death from any cause in patients with atrial fibrillation/atrial flutter) at the Venice Arrhythmias conference, held in Venice, Italy (4–7 October 2009).
“Results of these substudies are hypothesis-generating and help to determine the clinical value of dronedarone,” said Hohnloser.
The data showed by Hohnloser in Venice and also at the Europe AF conference (London, UK) in September was published in the 29 September 2009 issue of Circulation. The results showed that the addition of dronedarone (Multaq, Sanofi-aventis) to antithrombotic therapy and heart rate control reduced the risk of total strokes by 34% compared to the group who received placebo.
ATHENA is the largest antiarrhythmiac drug trial in atrial fibrillation. Patients with persistent or paroxysmal atrial fibrillation and at least one risk factor for cardiovascular hospitalisation were randomised to receive dronedarone (400 mg BID) or double-blind matching placebo and followed up for a minimum of one year to a common termination at 30 months. All strokes that occurred during the study were included in the present post hoc analysis. There were 4,628 patients randomised to placebo or dronedarone. The baseline risk factors for stroke were well balanced between the two groups, and the baseline mean CHADS2 score was 2. The baseline use of either oral anticoagulant therapy or antiplatelet agent alone was 60%. Dronedarone reduced the risk of stroke from 1.8% per year to 1.2% per year (hazard ratio 0.66, 95% confidence interval 0.46 to 0.96, p=0.027).
The effect of dronedarone was similar whether or not patients were receiving oral anticoagulant therapy, and there was a significantly greater effect of dronedarone in patients with higher CHADS2 scores.
The ATHENA trial showed that dronedarone in addition to standard therapy, reduced the combined endpoint of cardiovascular hospitalisation or death from any cause by 24% (p<0.001) when compared to placebo, meeting the study’s primary endpoint. Reported significant adverse events in the Multaq arm included diarrhoea, nausea, bradycardia, QT-interval prolongation and cutaneous rash.
Data presented by Hohnloser also showed that patients with stable class III congestive heart failure at baseline derived similar benefit from dronedarone than the overall population.
Further studies to investigate the effect of dronedarone and other antiarrhythmic agents on stroke are indicated, Hohnloser said.
Dronedarone recommended for approval in the European Union
On 25 September 2009 the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending granting a marketing authorisation in the European Union for Multaq. The CHMP has recommended the approval of Multaq in adult clinically stable patients with history of, or current non-permanent atrial fibrillation to prevent recurrence of atrial fibrillation or to lower ventricular rate.
In the Summary of Positive Opinion, the CHMP has acknowledged that dronedarone has been shown, in addition to its rhythm and rate controlling properties, to decrease the risk of atrial fibrillation-related hospitalisations. The positive opinion from the CHMP needs now to be ratified by the European Commission.
Multaq has recently received approval from the FDA, Health Canada and Swissmedic (Swiss Health Authority).