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 We included previously unpublished cancer outcome data from 1 RCT.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.