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New England Journal of Medicine

Clinical Articles, News & Views

PALLAS trial on dronedarone in AF now published

Dronedarone increases rates of serious vascular events in patients with permanent atrial fibrillation (AF) and additional cardiovascular risk factors, according to the PALLAS (Permanent Atrial Fibrillation Outcome Study Using Dronedarone on Top of Standard Therapy) trial1 published recently in the New England Journal of Medicine.

Researchers assigned patients from 37 countries who were at least 65 years of age, with a history of permanent AF and other risk factors for major vascular events, to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalisation for a cardiovascular cause or death.

After the enrollment of 3,236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone

and 19 receiving placebo (p=0.002).  There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group, including death from arrhythmia in 13 patients and 4 patients, respectively.  The increase in the rate of death from cardiovascular causes was mostly due to a substantial increase in the rate of death associated with arrhythmia.

Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group, while hospitalisation for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group.

Contrary to the authors’ hypothesis that dronedarone would reduce major vascular events in the patients, they found that it increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent AF who were at risk for major vascular events. The authors recommend that “dronedarone should be avoided in patients with heart failure and other advanced cardiovascular disease, particularly when they also have permanent AF”.

To explain the trial’s results, they hypothesise that “for high-risk patients with permanent AF, direct and indirect toxic effects of dronedarone are not offset by the benefit of maintaining sinus rhythm, and any benefits that might occur from heart-rate slowing, blood-pressure reduction, antiadrenergic action, and suppression of ventricular arrhythmia were either small or nonexistent”.


1 Connolly SJ, Camm J, Halperin JL, et al.  Dronedarone in high-risk permanent atrial fibrillation. N Engl J Med 2011. doi:10.1056/nejmoa1109867.

Published on: December 1, 2011

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