Chronic Amiodarone Use and the Risk of Cancer: A Systematic Review and Meta-analysis

BACKGROUND: Observational studies have identified inconsistent associations between chronic use of amiodarone and cancer-related outcomes. We performed a systematic review and meta-analysis to evaluate cancer risk among patients receiving amiodarone. METHODS: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) to May 1, 2020. We included randomized controlled trials (RCTs) with follow-up ≥2 years that compared amiodarone (any dose) to any comparator (placebo, active pharmacologic or interventional comparator, or usual care), and reported ≥1 outcome of interest. We contacted authors of published chronic amiodarone trials for potentially unreported cancer outcomes. The primary outcome was cancer incidence. Secondary outcomes were cancer-related death and site-specific cancers. We determined risk ratios and 95% confidence intervals using a fixed-effect model, and statistical heterogeneity using I(2). We conducted prespecified subgroup and sensitivity analyses for amiodarone indication, amiodarone dose, duration of therapy, and trial-level risk of bias. RESULTS: From 1439 articles, we included 5 RCTs (n = 4357). Mean follow-up duration ranged from 21 to 37 months. We included previously unpublished cancer outcome data from 1 RCT. Our primary outcome was not reported in any RCT. There was no significant difference in cancer-related death between amiodarone (1.69%) and the comparator (1.75%) (risk ratio 0.96, 95% confidence interval 0.57-1.63; I(2) = 0%). There were no significant interactions from our subgroup or sensitivity analyses. CONCLUSIONS: Chronic amiodarone use did not increase cancer-related deaths. Data from RCTs do not support an increased risk of cancer-related harms with amiodarone use, and these concerns should not deter use of amiodarone when indicated.