Amiodarone treatment in atrial fibrillation and the risk of incident cancers: A nationwide observational study

BACKGROUND In observational studies, case reports, and animal studies, amiodarone has been associated with incident cancer. OBJECTIVE The purpose of this study was to examine whether a dose-response relationship between amiodarone use and the risk of cancer could be ascertained in a large nationwide study cohort. METHODS Using nationwide registers, we included all Danish patients with atrial fibrillation (AF) treated with amiodarone from 1996 to 2014. Exposure was defined both by categories and as a continuous variable of the cumulative defined daily doses (cDDDs) of amiodarone. The associations between amiodarone cDDD and incident cancer, as well as organ-specific types of cancer (skin, liver, lung), were estimated using multivariable Cox regression models and reported as hazard ratios (HR) with 95% confidence intervals (CI) and using cubic restricted spline plots. RESULTS We included 18,503 patients with a median follow-up time of 8.1 years (interquartile range [IQR] 4.3-12.4). Median age was 70 years (IQR 63-77). A total of 2974 individuals developed cancer during follow-up. We found no association between increasing amiodarone exposure (cDDD 181-400 and cDDD >400) and the hazard of incident cancer (HR 0.95; 95% CI 0.87-1.04; and HR 1.01; 95% CI 0.92-1.10) with reference to patients with cDDD <181. Similar results were found when investigating specific cancer types (skin, liver, and lung) as well as cDDD as a continuous variable. CONCLUSION In a large nationwide cohort of AF patients treated with amiodarone, we found no evidence of a dose-response relationship between cumulative dose of amiodarone and incident cancer risk.