Liang Cuilv, Chen Qiying, Zhang Yin
Department of Pharmacy, Second Affiliated Hospital, Fujian Medical University, Quanzhou, China.
Second Affiliated Hospital, Fujian Medical University, 950 Donghai Street, Quanzhou, Fujian 362000, China.
Ther Adv Drug Saf. 2024 Jan 27;15:20420986231224236. doi: 10.1177/20420986231224236. eCollection 2024.
Studies have shown conflicting results when using thrombopoietin-related drugs (TPORD) for thromboembolic events (TEEs). Our study aimed to explore the correlation between TPORDs and TEEs.
Drug-targeted Mendelian randomization (MR) and multivariate MR (MVMR) analysis were used to explore the causal relationship between TPORDs and TEEs such as venous thromboembolism (VTE), deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI) and ischemic stroke (STR). At the same time, a real-world study was conducted by extracting adverse events (AEs) from the FDA Adverse Event Reporting System database included in AERSMine to further validate our findings.
In drug-target MR, TPORDs were associated with VTE (OR = 1.193, 95% confidence interval (CI): 1.001-1.423, = 0.049], DVT (OR = 1.321, 95% CI: 1.027-1.700, = 0.030), MI (OR = 1.216, 95% CI: 1.010-1.464, = 0.039), STR (OR = 1.224, 95% CI: 1.021-1.468, = 0.029). VTE/DVT/STR remained stable in MVMR (VTE: OR = 1.3, 95% CI: 1.187-1.422, < 0.001; DVT: OR = 1.465,95% CI:1.285-1.671, < 0.001; STR: OR = 1.119, 95% CI: 1.018-1.229, = 0.019) and real-world studies [lower bound of proportional reporting ratio (ROR) greater than 1]. The significance of myocardial infarction disappeared in MVMR (OR = 0.996, 95% CI: 0.894-1.109, = 0.942) and in real-world studies (lower ROR lower than 1). There was no evidence of a causal relationship between TPORD and PE (OR = 1.244, 95% CI: 0.969-1.597, = 0.087), but it generated a signal from a real-world study (lower bound of ROR greater than 1).
This study suggests that TPORDs may be associated with an increased risk of TEEs, particularly AEs leading to VTE/DVT/STR. In addition, the relationship between TPORDs and PE/MI is debatable and requires more research.
关于使用血小板生成素相关药物（TPORD）治疗血栓栓塞事件（TEE）的研究结果相互矛盾。我们的研究旨在探讨TPORD与TEE之间的相关性。
采用药物靶向孟德尔随机化（MR）和多变量MR（MVMR）分析，以探究TPORD与诸如静脉血栓栓塞（VTE）、深静脉血栓形成（DVT）、肺栓塞（PE）、心肌梗死（MI）和缺血性中风（STR）等TEE之间的因果关系。同时，通过从AERSMine中包含 的FDA不良事件报告系统数据库提取不良事件（AE）进行一项真实世界研究，以进一步验证我们的研究结果。
在药物靶向MR中，TPORD与VTE（比值比[OR]=1.193，95%置信区间[CI]：1.001-1.423，P=0.049）、DVT（OR=1.321，95%CI：1.027-1.700，P=0.030）、MI（OR=1.216，95%CI：1.010-1.464，P=0.039）、STR（OR=1.224，95%CI：1.021-1.468，P=0.029）相关。VTE/DVT/STR在MVMR（VTE：OR=1.3，95%CI：1.187-1.422，P<0.001；DVT：OR=1.465，95%CI：1.285-1.671，P<0.001；STR：OR=1.119，95%CI：1.018-1.229，P=）和真实世界研究[比例报告比（ROR）下限大于1]中保持稳定。心肌梗死的相关性在MVMR（OR=0.996，95%CI：0.894-1.109，P=0.942）和真实世界研究（ROR下限低于1）中消失。没有证据表明TPORD与PE之间存在因果关系（OR=1.244，95%CI：0.969-1.597，P=0.087），但它在真实世界研究中产生了一个信号（ROR下限大于1）。
本研究表明，TPORD可能与TEE风险增加相关，尤其是导致VTE/DVT/STR的不良事件。此外，TPORD与PE/MI之间的关系存在争议，需要更多研究。
