The use of digoxin in atrial fibrillation has remained controversial because of its narrow therapeutic window and its possible contribution to ventricular tachyarrhythmias and severe bradyarrhythmias. A study published in the journal Circulation: Arrhythmia and Electrophysiology reviews the outcomes of the Permanent Atrial Fibrillation Outcome Study Using Dronedarone On Top Of Standard Therapy (PALLAS), where researchers discovered an increase in both cardiovascular death and heart failure in patients receiving dronedarone therapy in addition to digoxin. 

Dronedarone is an antiarrythmic agent indicated to reduce the risk of hospitalization for atrial fibrillation in patients in sinus rhythm with a history of paroxysmal or persistant atrial fibrillation. When given together, dronedarone has been shown to increase the concentrations of digoxin via P-glycoprotein interaction. 

In the PALLAS study, 1,619 patients (544 were receiving digoxin) were randomized to dronedarone, while 1,617 patients (526 were receiving digoxin) were given placebo.  Among patients receiving digoxin at baseline, 15 cardiovascular deaths and 11 arrhythmic deaths occurred in the dronedarone group versus two cardiovascular deaths and no arrhythmic deaths in the placebo group. Among the patients who did not receive digoxin at baseline, six cardiovascular deaths and two arrhythmic deaths occurred in the dronedarone group versus eight cardiovascular deaths and four arrhythmic deaths in the placebo group. A significant increase in non-hospitalized heart failure events and heart failure hospitalizations were seen in the dronedarone group, however there was no evidence to that the dronedarone-digoxin interaction led to the development of heart failure.

Based on these findings, the authors conclude that while the concurrent use of digoxin and dronedarone does not appear to increase the occurrence of heart failure, there is a significant effect of digoxin use on the hazard of dronedarone for cardiovascular death.  The authors note that the study data is consistent with other studies which question whether digoxin should be used for rate control in atrial fibrillation.

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