Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine and School of Medicine, Seoul, South Korea.
Data Science Team, Hanmi Pharm. Co., Ltd, Seoul, South Korea.
Front Endocrinol (Lausanne). 2021 Oct 8;12:761782. doi: 10.3389/fendo.2021.761782. eCollection 2021.
Optimal treatment for persistent Graves' disease following 12-18 months of treatment with anti-thyroid drugs (ATDs) is unclear. Given the increased risk of cardiovascular morbidity and mortality with hyperthyroidism, assessing the risk of cardiovascular events associated with different treatment modalities after the conventional ATD course would be valuable in determining the appropriate next-line therapy.
This retrospective cohort study included data from the Korean National Health Insurance database of 16,882 patients with newly diagnosed hyperthyroidism who received primary ATD treatment for 24 months. Patients were categorized based on the treatment they received after receiving ATD for 24 months: continued ATD for at least 12 more months (ATD group), radioiodine ablation (RIA) with remission (RIA group 1), and RIA without remission (RIA group 2). The incidence and risk of heart failure (HF), the leading cause of cardiovascular mortality in hyperthyroidism, were compared between patients and age-and sex-matched controls.
There were 16,516 (97.8%) patients in the ATD group, 230 (1.4%) in RIA group 1, and 136 (0.8%) in RIA group 2. Compared to that of controls, a significant difference in the cumulative incidence of HF was observed according to second-line treatment modality after adjusting for covariates; the risk was highest in patients in RIA group 2, with a hazard ratio (HR) of 2.54 (95% confidence interval (CI) 1.60-4.03), followed by those in the ATD group, with an HR of 1.23 (95% CI 1.20-1.36). Patients in RIA group 1 were not at an increased risk of HF compared to their matched controls (HR 0.77; 95% CI 0.38-1.54). When patients in the ATD group were further classified by the duration of ATD treatment at one-year intervals, the risk of HF was higher in patients with longer ATD use (p for linear trend < 0.001).
In patients with long-standing hyperthyroidism treated with conventional duration of ATD therapy, the risk of HF was attenuated by RIA with remission of hyperthyroidism and increased as ATD was required for longer duration. To reduce the risk of HF, resolution of hyperthyroidism with RIA should be considered in patients with long-standing Graves' disease.
抗甲状腺药物（ATD）治疗 12-18 个月后持续性格雷夫斯病的最佳治疗方法尚不清楚。鉴于甲状腺功能亢进症患者心血管发病率和死亡率增加，评估常规 ATD 疗程后不同治疗方法与心血管事件相关的风险对于确定适当的下一线治疗方法将是有价值的。
本回顾性队列研究纳入了韩国国家健康保险数据库中 16882 名新诊断为甲状腺功能亢进症的患者数据，这些患者接受了为期 24 个月的原发性 ATD 治疗。根据接受 ATD 治疗 24 个月后的治疗方式，患者分为以下几类：继续接受 ATD 治疗至少 12 个月以上（ATD 组）、放射性碘消融（RIA）伴缓解（RIA 组 1）和 RIA 不缓解（RIA 组 2）。比较患者和年龄、性别匹配的对照组之间心力衰竭（HF）的发生率和风险，HF 是甲状腺功能亢进症心血管死亡率的主要原因。
ATD 组有 16516（97.8%）例患者，RIA 组 1 有 230（1.4%）例患者，RIA 组 2 有 136（0.8%）例患者。在校正了协变量后，根据二线治疗方式，与对照组相比，HF 的累积发生率存在显著差异；在 RIA 组 2 中风险最高，风险比（HR）为 2.54（95%置信区间（CI）为 1.60-4.03），其次是 ATD 组，HR 为 1.23（95%CI 为 1.20-1.36）。与匹配的对照组相比，RIA 组 1 的患者 HF 风险无增加（HR 0.77；95%CI 0.38-1.54）。当按 ATD 治疗时间以一年为间隔进一步对 ATD 组患者进行分类时，ATD 治疗时间较长的患者 HF 风险更高（p 趋势<0.001）。
在接受常规 ATD 治疗时间较长的甲状腺功能亢进症患者中，RIA 缓解甲状腺功能亢进症可降低 HF 风险，而 ATD 治疗时间延长则会增加 HF 风险。为降低 HF 风险，应考虑在长期格雷夫斯病患者中使用 RIA 来缓解甲状腺功能亢进症。
