目的 借助加拿大藥物警戒不良事件在線數(shù)據(jù)庫（CVARD）和美國食品藥品監(jiān)督管理局不良事件報(bào)告系統(tǒng)（FAERS）挖掘和分析他汀類藥物與甲狀腺不良事件的關(guān)聯(lián)性，為臨床安全用藥提供參考。方法 收集CVARD數(shù)據(jù)庫1991年1月—2024年6月，F(xiàn)AERS數(shù)據(jù)庫2004年第一季度—2024年第二季度期間接收到的他汀類藥物相關(guān)的甲狀腺不良事件的報(bào)告。采用報(bào)告比值比法（ROR）、比例報(bào)告比值比法（PRR）和貝葉斯置信區(qū)間傳播神經(jīng)網(wǎng)絡(luò)法（BCPNN）檢測他汀類藥物的風(fēng)險(xiǎn)信號。結(jié)果 共檢索到他汀類藥物相關(guān)的甲狀腺不良事件253例，其中阿托伐他汀、瑞舒伐他汀、普伐他汀、氟伐他汀的報(bào)告數(shù)分別為129、111、10、3例；檢測發(fā)現(xiàn)了阿托伐他汀相關(guān)的甲狀腺癌、甲狀腺腫和甲狀腺疾病3個(gè)不良事件風(fēng)險(xiǎn)信號，瑞舒伐他汀相關(guān)的甲狀腺腫、甲狀腺疾病和促甲狀腺激素升高3個(gè)風(fēng)險(xiǎn)信號，普伐他汀相關(guān)的甲狀腺功能減退不良事件風(fēng)險(xiǎn)信號，氟伐他汀相關(guān)的自身免疫性甲狀腺炎不良事件風(fēng)險(xiǎn)信號。在FAERS數(shù)據(jù)庫中，氟伐他汀相關(guān)的自身免疫性甲狀腺炎風(fēng)險(xiǎn)信號最高（ROR＝23.074）；在CVARD數(shù)據(jù)庫中，普伐他汀相關(guān)的甲狀腺功能減退風(fēng)險(xiǎn)信號最高（ROR＝13.66）。檢索發(fā)現(xiàn)甲狀腺不良事件在用藥后31～90 d內(nèi)誘發(fā)的病例占比最大（65.4%），使用阿托伐他汀的女性患者表現(xiàn)出更高的甲狀腺疾病、甲狀腺腫和甲狀腺癌風(fēng)險(xiǎn)信號，而使用瑞舒伐他汀的男性患者則更易出現(xiàn)甲狀腺疾病、甲狀腺腫和促甲狀腺激素升高的風(fēng)險(xiǎn)信號。誘發(fā)甲狀腺不良事件的阿托伐他汀和氟伐他汀的累積日劑量平均數(shù)和最大劑量均在我國藥品說明書正常范圍內(nèi)，但是瑞舒伐他汀和普伐他汀相關(guān)累積日劑量均超過我國藥品說明書最大劑量范圍。結(jié)論 對FAERS/CVARD數(shù)據(jù)庫的藥物警戒分析顯示，阿托伐他汀、瑞舒伐他汀和氟伐他汀與甲狀腺不良事件的風(fēng)險(xiǎn)存在一定關(guān)聯(lián)。

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

國家自然科學(xué)基金青年科學(xué)基金項(xiàng)目（82405004）