A reduction in stroke was observed in patients with atrial fibrillation who were receiving usual care, which included antithrombotic therapy and heart rate control, and were randomized to dronedarone (Multaq, Sanofi-Aventis), according to a post-hoc analysis of the ATHENA trial, published Sept. 10 online in Circulation.
Many patients with atrial fibrillation are at high risk for stroke and require antithrombotic therapy, requiring hospitalizations. However, antiarrhythmic drugs have not previously been shown to reduce the risk of stroke in atrial fibrillation, according to Stuart J. Connolly, MD, from McMaster University in Hamilton, Ontario, and the other ATHENA investigators.
The effect of dronedarone, a newly FDA-approved 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).
In the trial, patients with persistent or paroxysmal atrial fibrillation and at least one 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 one year to a common termination at 30 months.
The researchers included all strokes that occurred during the study in the present post-hoc analysis. There were 4,628 patients randomized to placebo or dronedarone.
According to the authors, the baseline risk factors for stroke were “well balanced between the two groups,” and the baseline mean CHADS2 score was two. The baseline use of either oral anticoagulant therapy or antiplatelet agent alone was 60 percent.
Connolly and colleagues found that dronedarone reduced the risk of stroke from 1.8 percent per year to 1.2 percent per year.
“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,” they wrote.
Strokes related to hospitalizations were reported as hemorrhagic or ischemic strokes. The number of hemorrhagic strokes was the same: six (annual rate 0.2 percent) with placebo and six (annual rate 0.2 percent) with dronedarone therapy, the researchers reported. However, the risk of ischemic stroke was 0.9 percent per year with dronedarone and 1.3 percent with placebo.
Because it has not previously been found, the authors wrote, “observation in the present study that an antiarrhythmic drug may have had an effect against stroke is therefore both novel and important, reopening the possibility that either pharmacological or nonpharmacological suppression of AF could have a beneficial effect on stroke.”
However, it should be noted that the ATHENA trial was not powered for this analysis, and must be confirmed by future trials.
The trial was sponsored by Sanofi-Aventis and designed by a steering committee in collaboration with the sponsor.