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Interaction between digoxin and dronedarone in the PALLAS trial.

Publication ,  Journal Article
Hohnloser, SH; Halperin, JL; Camm, AJ; Gao, P; Radzik, D; Connolly, SJ; PALLAS investigators,
Published in: Circ Arrhythm Electrophysiol
December 2014

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. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01151137.

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Published In

Circ Arrhythm Electrophysiol

DOI

EISSN

1941-3084

Publication Date

December 2014

Volume

7

Issue

6

Start / End Page

1019 / 1025

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Time Factors
  • Risk Factors
  • Proportional Hazards Models
  • Male
  • Kaplan-Meier Estimate
  • Humans
  • Heart Failure
  • Female
  • Electrocardiography
 

Citation

APA
Chicago
ICMJE
MLA
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Hohnloser, S. H., Halperin, J. L., Camm, A. J., Gao, P., Radzik, D., Connolly, S. J., & PALLAS investigators, . (2014). Interaction between digoxin and dronedarone in the PALLAS trial. Circ Arrhythm Electrophysiol, 7(6), 1019–1025. https://doi.org/10.1161/CIRCEP.114.002046
Hohnloser, Stefan H., Jonathan L. Halperin, A John Camm, Peggy Gao, David Radzik, Stuart J. Connolly, and Stuart J. PALLAS investigators. “Interaction between digoxin and dronedarone in the PALLAS trial.Circ Arrhythm Electrophysiol 7, no. 6 (December 2014): 1019–25. https://doi.org/10.1161/CIRCEP.114.002046.
Hohnloser SH, Halperin JL, Camm AJ, Gao P, Radzik D, Connolly SJ, et al. Interaction between digoxin and dronedarone in the PALLAS trial. Circ Arrhythm Electrophysiol. 2014 Dec;7(6):1019–25.
Hohnloser, Stefan H., et al. “Interaction between digoxin and dronedarone in the PALLAS trial.Circ Arrhythm Electrophysiol, vol. 7, no. 6, Dec. 2014, pp. 1019–25. Pubmed, doi:10.1161/CIRCEP.114.002046.
Hohnloser SH, Halperin JL, Camm AJ, Gao P, Radzik D, Connolly SJ, PALLAS investigators. Interaction between digoxin and dronedarone in the PALLAS trial. Circ Arrhythm Electrophysiol. 2014 Dec;7(6):1019–1025.

Published In

Circ Arrhythm Electrophysiol

DOI

EISSN

1941-3084

Publication Date

December 2014

Volume

7

Issue

6

Start / End Page

1019 / 1025

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Time Factors
  • Risk Factors
  • Proportional Hazards Models
  • Male
  • Kaplan-Meier Estimate
  • Humans
  • Heart Failure
  • Female
  • Electrocardiography