Antiarrhythmic Agents and the Risk of Malignant Neoplasm of Liver and Intrahepatic Bile Ducts

Abstract

BackgroundThe 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).MethodsWe 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.ResultsThe 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.ConclusionsThe 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.

Gastrointestinal Side Effects of Antiarrhythmic Medications: A Review of Current Literature

“…A large retrospective cohort study conducted in Taiwan showed that use of amiodarone is associated with malignant neoplasm of the liver and intrahepatic bile ducts (MNLIHD) in a dose-dependent manner. Malignancy is common in cases with comorbidities, such as diabetes, chronic liver disease, cirrhosis, hepatitis C, hepatitis B, and alcoholism (Table 7 ) [ 36 ].…”

Atrial fibrillation and cancer; understanding the mysterious relationship through a systematic review

“…Similarly, in the study by Lim et al Amiodarone was associated with an increased risk of malignant neoplasm of liver and intrahepatic bile ducts with an odds ratio of 1.60 (1.-45-1.77). The latter study also found an association of increased risk of cancer with other antiarrhythmic medications like Quinidine and Propafenone; however, the adjusted ratios were not significant for these two drugs [17,24]. Few case reports have described hepatotoxicity arising from the use of Propafenone.…”

Association Between Digoxin Use and Cancer Incidence: A Propensity Score-Matched Cohort Study With Competing Risk Analysis

“…Moreover, digoxin use showed increased the risk of colorectal, lung, and uterine cancers analyzing the database in Denmark and the United Kingdom (Biggar et al, 2012;Boursi et al, 2014;Couraud et al, 2014b). On the contrary, studies from Sweden, Ireland, and Taiwan indicated that digoxin decreased the risk of prostate and liver cancers (Flahavan et al, 2014;Lim et al, 2015;Xie et al, 2017). The meta-analyses make a great effort to pool twenty-seven studies that showed digoxin increased the risk of estrogen receptor-positive breast cancer but not others (Osman et al, 2017); however, the heterogeneity of the previous studies might limit the data interpretation.…”