Siemers Lauren A, MacGillivray Jenny, Andrade Jason G, Turgeon Ricky D
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Atrial Fibrillation Clinic, Vancouver General Hospital, Vancouver, British Columbia, Canada.
CJC Open. 2020 Sep 17;3(1):109-114. doi: 10.1016/j.cjco.2020.09.013. eCollection 2021 Jan.
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.
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 . We conducted prespecified subgroup and sensitivity analyses for amiodarone indication, amiodarone dose, duration of therapy, and trial-level risk of bias.
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 We included previously unpublished cancer outcome data from 1 RCT.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; = 0%). There were no significant interactions from our subgroup or sensitivity analyses.
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.
观察性研究发现，长期使用胺碘酮与癌症相关结局之间的关联并不一致。我们进行了一项系统评价和荟萃分析，以评估接受胺碘酮治疗的患者的癌症风险。
我们检索了截至2020年5月1日的MEDLINE、Embase和Cochrane对照试验中央注册库（CENTRAL）。我们纳入了随访时间≥2年的随机对照试验（RCT），这些试验将胺碘酮（任何剂量）与任何对照（安慰剂、活性药物或介入性对照或常规治疗）进行比较，并报告了≥1项感兴趣的结局。我们联系了已发表的慢性胺碘酮试验的作者，以获取可能未报告的癌症结局。主要结局是癌症发病率。次要结局是癌症相关死亡和特定部位癌症。我们使用固定效应模型确定风险比和95%置信区间，并使用 确定统计异质性。我们针对胺碘酮适应症、胺碘酮剂量、治疗持续时间和试验水平的偏倚风险进行了预先设定的亚组分析和敏感性分析。
从1439篇文章中，我们纳入了5项RCT（n = 4357）。平均随访时间为21至37个月。我们纳入了1项RCT中以前未发表的癌症结局数据。我们的主要结局在任何RCT中均未报告。胺碘酮组（1.69%）和对照组（1.75%）之间的癌症相关死亡没有显著差异（风险比0.96，95%置信区间0.57 - 1.63； = 0%）。我们的亚组分析或敏感性分析没有显著的相互作用。
长期使用胺碘酮不会增加癌症相关死亡。RCT的数据不支持使用胺碘酮会增加癌症相关危害的风险，并且在有指征时，这些担忧不应妨碍胺碘酮的使用。
