Analysis of stroke in ATHENA: 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.

BACKGROUND: Many patients with atrial fibrillation are at high risk for stroke and require antithrombotic therapy. Antiarrhythmic drugs have not previously been shown to reduce the risk of stroke in atrial fibrillation. The effect of dronedarone, a new multichannel-blocking antiarrhythmic drug, on stroke has been evaluated in a randomized, double-blind clinical trial, ATHENA (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).

METHODS AND RESULTS: Patients with persistent or paroxysmal atrial fibrillation and at least 1 risk factor for cardiovascular hospitalization were randomized to receive dronedarone (400 mg BID) or double-blind matching placebo and followed up for a minimum of 1 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 4628 patients randomized to placebo or dronedarone. The baseline risk factors for stroke were well balanced between the 2 groups, and the baseline mean CHADS(2) 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 CHADS(2) scores.

CONCLUSIONS: In this post hoc analysis, a reduction in stroke was observed in patients with atrial fibrillation who were receiving usual care, which included antithrombotic therapy and heart rate control, who were randomized to dronedarone. Further studies to investigate the effect of dronedarone and other antiarrhythmic agents on stroke are indicated.