Background: Amiodarone is rich in iodine, so in clinical practice amiodarone-induced hypothyroidism (AIH) is a major side effect. This drug is used in patients with arrhythmias, especially atrial fibrillation, the most common sustained arrhythmia. Polypharmacy, which can result in complex drug-drug interactions, occurs in more than 70% of the patients with atrial fibrillation. Therefore, polypharmacy may be involved in the expression of AIH. In this study, we investigated the association between polypharmacy and AIH. Methods: We conducted a retrospective study using data from January 2006 to May 2020 collected from a large, organized database of prescriptions constructed by the Japan Medical Information Research Institute, Inc. (Tokyo, Japan). To investigate the association between number of prescribed drugs with amiodarone and AIH, we divided patients into two groups: polypharmacy (≥ 5 prescribed drugs) and non-polypharmacy (< 5 prescribed drugs). We then performed a sequence symmetry analysis on the two groups: incident thyroxine after incident amiodarone and incident thyroxine before incident amiodarone. Finally, we conducted a case-control study on two further groups: those prescribed thyroxine after incident amiodarone (AIH group; n=555) and those not prescribed thyroxine after incident amiodarone (non-AIH group; n=6,192). Results: Sequence symmetry analysis revealed a significant association between amiodarone and thyroxine in both the polypharmacy and non-polypharmacy groups. The ranges for the adjusted sequence ratio in the two groups were 12.0-16.7 and 7.3-9.0, respectively. The case-control study showed that ≥5 prescribed drugs at the first prescription of amiodarone were found to significantly increase the odds of AIH (odds ratio: 1.48, 95% confidence interval: 1.18-1.84). Conclusion: Polypharmacy was suggested as an independent risk factor for AIH. Careful assessment of the appropriateness of prescription is warranted.

中文翻译：

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多药治疗与胺碘酮诱发的甲状腺功能减退症有关。

背景：胺碘酮富含碘，因此在临床实践中胺碘酮诱发的甲状腺功能减退症（AIH）是主要的副作用。这种药物用于心律失常患者，尤其是心房颤动，这是最常见的持续性心律失常。超过 70% 的心房颤动患者会出现多种药物治疗，这会导致复杂的药物间相互作用。因此，多种药物可能参与了 AIH 的表达。在这项研究中，我们调查了多种药物治疗与 AIH 之间的关联。方法：我们使用从日本医学信息研究所（日本东京）构建的大型、有组织的处方数据库中收集的 2006 年 1 月至 2020 年 5 月的数据进行了一项回顾性研究。调查处方药数量与胺碘酮和 AIH 之间的关系，我们将患者分为两组：多药组（≥ 5 种处方药）和非多药组（< 5 种处方药）。然后，我们对两组进行了序列对称性分析：事件胺碘酮之后的事件甲状腺素和事件胺碘酮之前的事件甲状腺素。最后，我们对另外两组进行了病例对照研究：发生胺碘酮后开具甲状腺素的组（AIH 组；n=555）和发生胺碘酮后未开具甲状腺素的组（非 AIH 组；n=6,192）。结果：序列对称性分析揭示了胺碘酮和甲状腺素在多药组和非多药组中的显着关联。两组调整序列比的范围分别为12.0-16.7和7.3-9.0。病例对照研究表明，首次处方胺碘酮时≥5 种处方药可显着增加 AIH 的几率（优势比：1.48，95% 置信区间：1.18-1.84）。结论：建议使用多种药物作为 AIH 的独立危险因素。有必要仔细评估处方的适当性。