Why the study?
Does dronedarone reduce major vascular events in patients ≥65 years with high-risk permanent atrial fibrillation?
Does dronedarone reduce major vascular events in patients ≥65 years with high-risk permanent atrial fibrillation?
Dronedarone increases the risk of cardiovascular death, stroke, and heart failure in patients with permanent atrial fibrillation and is contraindicated in this population.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Approximately 70% of patients in PALLAS had AF of over 2 year's duration and approximately the same percentage had heart failure sufficiently severe to warrant hospitalization in the prior year – though not in the prior month. Advanced structural heart disease, worsened ventricular function and its consequences while on dronedarone rather than on placebo during periods of decompensation, and adverse dronedarone-digoxin interactions were likely major factors in the outcome results in PALLAS.”
“Surprisingly, an increased rate of stroke (HR 2.32 95% CI 1.11-4.88, p=0.02) was also found among patients receiving dronedarone, which had not been found in prior subset analysis of similar patients enrolled in ATHENA.”
“Many investigators commented that patients with permanent atrial fibrillation felt reasonably well and did not want to take part in a trial involving an additional medication.”
Contraindicates dronedarone in permanent atrial fibrillation; confirms harm and supports guideline prohibition.
BACKGROUND: Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation. METHODS: We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and 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 hospitalization for a cardiovascular cause or death. RESULTS: After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02). CONCLUSIONS: Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.).
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A 2011 study studied this question.
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