title: Antiarrhythmic agents and the risk of malignant neoplasm of liver and intrahepatic bile ducts.
abstract: 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.
authors.affiliation: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan; Department of Emergency, Toxicology Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Yun-Ping
authors.initials: YP
authors.lastname: Lim
authors.affiliation: Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Cheng-Li
authors.initials: CL
authors.lastname: Lin
authors.affiliation: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Yen-Ning
authors.initials: YN
authors.lastname: Lin
authors.affiliation: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan; Department of Pharmacy, National Cheng Kung University Hospital Dou-Liou Branch, Yunlin, Taiwan.
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan; Department of Emergency, Toxicology Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Dong-Zong
authors.initials: DZ
authors.lastname: Hung
authors.affiliation: Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Kao
mesh_terms: D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D001650:Bile Duct Neoplasms / Q000139:chemically induced*; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012306:Risk; D012307:Risk Factors; D013624:Taiwan; D055815:Young Adult
chemical_list: D000889:Anti-Arrhythmia Agents