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.

OBJECTIVES:

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.

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 (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.

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 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.

CONCLUSIONS:

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.