Metoprolol adverse events and literature analyses: case/non-case analyses using the FDA adverse event reporting system (FAERS)

In recent years, β-blockers such as metoprolol have been upgraded to first-line antihypertensive drugs. However, metoprolol demonstrates poor prognosis effects on diseases such as stroke. Further clinical application may expand the possibility of its related adverse reactions. Currently, there is a lack of comprehensive research on the overall safety of metoprolol. Statistical analysis and signal mining were conducted on adverse event reports related to metoprolol obtained from the FAERS database. Signal mining was conducted using the proportional reporting ratio, the report margin method, the bayesian confidence propagation neural network, and empirical Bayesian geometric mean in the measures of disproportionality to detect potential adverse reaction signals. The results showed 16,853 reports related to metoprolol use, identifying 506 preferred terms (PTs) covering 23 system organ classes (SOCs). In addition, some new potential adverse reactions appeared among the top 30 PTs ranked by signal strength, such as ‘orthostatic intolerance’ (IC025 = 3.00), ‘trigemino-cardiac reflex’ (IC025 = 4.30), ‘decorticate posture’ (IC025 = 3.34), etc. Notably, there was a strong association between ‘suspected suicide’ (IC025 = 5.59) and the drug signal. This study identified unexpected signals of serious adverse reactions, suggesting the importance of continuous post-marketing surveillance of metoprolol to understand its potential risks.

近年来，以美托洛尔为代表的β受体阻滞剂（β-blockers）已被升级为一线降压药物。然而，美托洛尔对脑卒中这类疾病的预后效果欠佳。随着其临床应用范围进一步扩大，相关不良反应的发生风险也可能随之提升。目前，针对美托洛尔整体安全性的全面研究仍较为匮乏。本研究对从FAERS数据库获取的美托洛尔相关不良事件报告开展了统计分析与信号挖掘。采用比例报告比值法、报告比值比法、贝叶斯置信传播神经网络法以及经验贝叶斯几何平均法等多种失衡性分析手段进行信号挖掘，以识别潜在的不良反应信号。研究结果显示，共计纳入16853条美托洛尔用药相关不良事件报告，共识别出506个首选术语（preferred terms, PTs），覆盖23个系统器官分类（system organ classes, SOCs）。此外，在按信号强度排序的前30个首选术语中，还发现了若干新的潜在不良反应，如“体位不耐受”（IC025=3.00）、“三叉神经心脏反射异常”（IC025=4.30）、“去皮质姿势”（IC025=3.34）等。值得注意的是，“疑似自杀”（IC025=5.59）与该药物信号存在较强的关联性。本研究识别出了美托洛尔相关严重不良反应的未预期信号，提示需持续开展美托洛尔上市后监测，以明确其潜在用药风险。