The present systematic review and meta- analysis of all available data sources suggest that digoxin use is associated with an increased mortality risk , particularly among patients suffering from AF
There are conflicting data regarding the effect of digoxin use on mortality in patients with atrial fibrillation ( AF ) or with congestive heart failure ( CHF ) .
The aim of this meta- analysis was to provide detailed analysis of the currently available study reports .
Interaction Between Digoxin and Dronedarone in the PALLAS Trial
Background —Elevated serum digoxin concentration can cause toxicity , including death .  Dronedarone increases digoxin concentration by P-glycoprotein interaction . In Permanent Atrial Fibrillation Outcome Study Using Dronedarone On Top Of St and ard Therapy Trial ( PALLAS ) , dronedarone was associated with both increased cardiovascular death and heart failure in patients with permanent atrial fibrillation . The present analysis examines whether the dronedarone – digoxin interaction might explain these adverse outcomes . Methods and Results —Subgroup analysis was performed to compare outcomes of patients on digoxin at baseline or not . In PALLAS , 1619 patients were r and omized to dronedarone and 1617 to placebo , of whom 544 ( 33.6 % ) and 526 ( 32.5 % ) were receiving digoxin , respectively .  Median ( Q1,Q3 ) digoxin serum concentration on day 7 was 1.1 ( 0.7,1.5 ) ng/mL on dronedarone and 0.7 ( 0.5,1.1 ) ng/mL on placebo ( P<0.001 ) . Among patients on digoxin , there were 15 ( 8.6%/year ) cardiovascular deaths on dronedarone and 2 ( 1.2%/year ) on placebo ( adjusted hazard ratio , 7.31 ; 95 % confidence interval , 1.66–32.20 ; P=0.009 ) . Among patients not on digoxin , there were 6 cardiovascular deaths on dronedarone ( 1.7%/year ) and 8 on placebo ( 2.2%/year ; adjusted hazard ratio , 0.67 ; 95 % confidence interval , 0.23–1.95 ; P=0.46 ; interaction P value 0.01 ) . In patients on digoxin , there were 11 arrhythmic deaths on dronedarone and none on placebo ; and in patients not on digoxin , there were 2 arrhythmic deaths on dronedarone and 4 on placebo ( P value for interaction 0.002 ) . There was no interaction between baseline digoxin use and the adverse effect of dronedarone on heart failure events . Conclusions —In PALLAS , there was a strong effect of concurrent digoxin use on the adverse effect of dronedarone on cardiovascular death , but not on occurrence of heart failure . Clinical Trial Registration —http://www . clinical trials.gov . Unique identifier : NCT01151137
The present systematic review and meta- analysis of all available data sources suggest that digoxin use is associated with an increased mortality risk , particularly among patients suffering from AF
There are conflicting data regarding the effect of digoxin use on mortality in patients with atrial fibrillation ( AF ) or with congestive heart failure ( CHF ) .
The aim of this meta- analysis was to provide detailed analysis of the currently available study reports .