目的 借助加拿大药物警戒不良事件在线数据库（CVARD）和美国食品药品监督管理局不良事件报告系统（FAERS）挖掘和分析他汀类药物与甲状腺不良事件的关联性，为临床安全用药提供参考。方法 收集CVARD数据库1991年1月—2024年6月，FAERS数据库2004年第一季度—2024年第二季度期间接收到的他汀类药物相关的甲状腺不良事件的报告。采用报告比值比法（ROR）、比例报告比值比法（PRR）和贝叶斯置信区间传播神经网络法（BCPNN）检测他汀类药物的风险信号。结果 共检索到他汀类药物相关的甲状腺不良事件253例，其中阿托伐他汀、瑞舒伐他汀、普伐他汀、氟伐他汀的报告数分别为129、111、10、3例；检测发现了阿托伐他汀相关的甲状腺癌、甲状腺肿和甲状腺疾病3个不良事件风险信号，瑞舒伐他汀相关的甲状腺肿、甲状腺疾病和促甲状腺激素升高3个风险信号，普伐他汀相关的甲状腺功能减退不良事件风险信号，氟伐他汀相关的自身免疫性甲状腺炎不良事件风险信号。在FAERS数据库中，氟伐他汀相关的自身免疫性甲状腺炎风险信号最高（ROR＝23.074）；在CVARD数据库中，普伐他汀相关的甲状腺功能减退风险信号最高（ROR＝13.66）。检索发现甲状腺不良事件在用药后31～90 d内诱发的病例占比最大（65.4%），使用阿托伐他汀的女性患者表现出更高的甲状腺疾病、甲状腺肿和甲状腺癌风险信号，而使用瑞舒伐他汀的男性患者则更易出现甲状腺疾病、甲状腺肿和促甲状腺激素升高的风险信号。诱发甲状腺不良事件的阿托伐他汀和氟伐他汀的累积日剂量平均数和最大剂量均在我国药品说明书正常范围内，但是瑞舒伐他汀和普伐他汀相关累积日剂量均超过我国药品说明书最大剂量范围。结论 对FAERS/CVARD数据库的药物警戒分析显示，阿托伐他汀、瑞舒伐他汀和氟伐他汀与甲状腺不良事件的风险存在一定关联。

Objective To analyze the risk signals of thyroid adverse events associated with statins by mining the Canada Vigilance Adverse Reaction Online Database (CVARD) and the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, so as to provide a reference for clinical safe drug use. Methods Reports on thyroid-related adverse events caused by statins received from January 1991 to June 2024 in the CVARD database and from the first quarter of 2004 to the second quarter of 2024 in the FAERS database were collected. The reporting odds ratio (ROR), proportional reporting ratio (PRR) and Bayesian confidence propagation neural network (BCPNN) were used to detect the risk signals of the above drugs. Results A total of 253 statin related thyroid adverse events were retrieved, including 129, 111, 10 and 3 reports of atorvastatin, rosuvastatin, pravastatin and fluvastatin, respectively. The test identified three adverse event risk signals for atorvastatin related thyroid cancer, goiter, and thyroid disease; three risk signals for rosuvastatin related goiter, thyroid disease, and thyrotropin elevation; and three risk signals for pravastatin related hypothyroidism. Risk signals for adverse events in autoimmune thyroiditis associated with fluvastatin. In the FAERS database, the risk signal of fluvastatin associated autoimmune thyroiditis was the highest (ROR = 23.074). In the CVARD database, pravastatin was associated with the highest hypothyroidism risk signal (ROR = 13.66). The largest proportion (65.4%) of adverse thyroid events were found to occur within 31—90 days of treatment. Women using atorvastatin showed higher risk signals for thyroid disease, goiter, and thyroid cancer, while men using rosuvastatin showed higher risk signals for thyroid disease, goiter, and elevated thyrotropin. The average and maximum cumulative daily dose of atorvastatin and fluvastatin were within the normal range of the drug label in China, but the cumulative daily dose related to rosuvastatin and pravastatin exceeded the maximum dose range of the drug label in China. Conclusion Pharmacovigilance analysis of FAERS/CVARD database showed that atorvastatin, rosuvastatin and fluvastatin were statistically associated with the risk of thyroid adverse events.

R972

国家自然科学基金青年科学基金项目（82405004）