In observational studies, case reports, and animal studies, amiodarone has been associated with incident cancer.
To examine whether a dose-response relationship between the use of amiodarone and the risk of cancer could be ascertained in a large nationwide study cohort.
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 (cDDD) of amiodarone. The association 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.
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 associations between increasing amiodarone exposure (cDDD 181-400 & cDDD >400) and the hazard of incident cancer (HR 0.95, 95% CI 0.87 – 1.04 & HR 1.01, 95% CI 0.92 – 1.10) with reference to patients with a cDDD < 181. When investigating specific cancer types (skin, liver, and lung), as well as cDDD as a continuous variable, similar results were found.
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.