Interaction between digoxin and dronedarone in the PALLAS trial

Hohnloser, Stefan H., Halperin, Jonathan L., Camm, A. John, Gao, Peggy, Radzik, David, Connolly, Stuart J., PALLAS investigators and Colquhoun, David (2014) Interaction between digoxin and dronedarone in the PALLAS trial. Circulation: Arrhythmia and Electrophysiology, 7 6: 1019-1025. doi:10.1161/CIRCEP.114.002046


Author Hohnloser, Stefan H.
Halperin, Jonathan L.
Camm, A. John
Gao, Peggy
Radzik, David
Connolly, Stuart J.
PALLAS investigators
Colquhoun, David
Title Interaction between digoxin and dronedarone in the PALLAS trial
Journal name Circulation: Arrhythmia and Electrophysiology   Check publisher's open access policy
ISSN 1941-3084
Publication date 2014-12-01
Sub-type Article (original research)
DOI 10.1161/CIRCEP.114.002046
Open Access Status Not yet assessed
Volume 7
Issue 6
Start page 1019
End page 1025
Total pages 7
Place of publication Philadelphia, United States
Publisher Lippincott Williams and Wilkins
Language eng
Formatted abstract
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 Standard 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 randomized 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.
Keyword Antiarrhythmic drug
Atrial fibrillation
Digoxin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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