Antiarrhythmic agents and the risk of malignant neoplasm of liver and intrahepatic bile ducts

PLoS One. 2015 Jan 15;10(1):e0116960. doi: 10.1371/journal.pone.0116960. eCollection 2015.


Background: The objective of this study was to determine the association between the use of antiarrhythmic agents and the risk of malignant neoplasm of liver and intrahepatic bile ducts (MNLIHD).

Methods: We used the research database of the Taiwan National Health Insurance Program to conduct a population-based, case-control study. We identified 9944 patients with antiarrhythmic history who were first diagnosed as having MNLIHD between 2005 and 2010. We identified an additional 19,497 patients with antiarrhythmic history in the same period who did not develop MNLIHD and were frequency-matched using age, sex, and index year to form a control group. Five commercially available antiarrhythmic agents, amiodarone, mexiletine, propafenone, quinidine, and procainamide, were analyzed.

Results: The adjusted odds ratio (OR) of MNLIHD was 1.60 (95% confidence interval [CI], 1.45-1.77) for amiodarone users versus nonamiodarone users. In subgroup analysis, amiodarone use was significantly associated with an increased risk of MNLIHD with an adjusted OR of 18.0 (95% CI, 15.7-20.5) for patients with comorbidities compared to an OR of 2.43 (95% CI, 1.92-3.06) for those without comorbidities. After adjustment for age, sex, statins, anti-diabetes medications, non-steroidal antiinflammatory drugs, propafenone use, quinidine use, and comorbidities, the ORs were 1.49, 1.66, and 1.79 for MNLIHD associated with annual mean defined daily doses of ≤ 30, 31-145, and >145, respectively.

Conclusions: The results of the present study indicated that amiodarone might be associated with the development of MNLIHD in a dose-dependent manner, particularly among patients with comorbidities.

MeSH terms

  • Adult
  • Aged
  • Anti-Arrhythmia Agents / adverse effects*
  • Bile Duct Neoplasms / chemically induced*
  • Bile Ducts, Intrahepatic / drug effects*
  • Case-Control Studies
  • Female
  • Humans
  • Liver Neoplasms / chemically induced*
  • Male
  • Middle Aged
  • Odds Ratio
  • Risk
  • Risk Factors
  • Taiwan
  • Young Adult


  • Anti-Arrhythmia Agents

Grants and funding

These authors have no support or funding to report.