Shi Fang-E, Yu Zhe, Sun Chengyue, Gao Peiliang, Zhang Haiyan, Zhu Jihong
Department of Emergency, Peking University People's Hospital, Beijing, China.
Peking University Ditan Teaching Hospital, Beijing, China.
Expert Opin Drug Saf. 2024 Feb;23(2):221-229. doi: 10.1080/14740338.2023.2245745. Epub 2023 Aug 18.
The aim of this study is to monitor, identify, and compare the adverse events (AEs) related to tenecteplase and alteplase, with the objective of exploring the potential safety of tenecteplase for acute ischemic stroke (AIS) and guiding its use to enhance patient safety.
In order to evaluate the disproportionality of AEs associated with tenecteplase and alteplase in real-world data, four algorithms (ROR, PRR, BCPNN, EBGM) were utilized as measures to detect signals of AEs related to both drugs. Subsequently, Breslow-Day statistical analysis was applied to compare the RORs of the main system organ classes (SOCs) and key preferred terms (PTs) between tenecteplase and alteplase.
A statistical analysis was performed utilizing data gleaned from the Food and Drug Administration Adverse Event Reporting System (FAERS) database, encompassing 19,514,140 case reports from 2004Q1 to 2023Q1. There were 1,004 cases where tenecteplase was reported as the primary suspected (PS) and 2,363 tenecteplase-related adverse drug reactions (ADRs) at the PTs level were identified, the two data of alteplase were 10,945 and 25,266, respectively. The occurrence of drug-induced ADRs was analyzed across 27 organ systems, The analysis revealed several expected ADRs, such as Haemorrhage, Hypersensitivity which were consistent with the two drug-labels. It is of note that the signal strengths of 'death,' 'ventricular fibrillation,' 'cardiogenic shock' and 'pneumonia aspiration' at the PT level were markedly higher for tenecteplase than for alteplase, whereas the signal strength of 'angioedema' at the PT level was significantly higher for alteplase in comparison to tenecteplase. Additionally, unexpected significant ADRs associated with ocular adverse reactions and pneumonia aspiration at the PT level were identified, indicating potential AEs not currently mentioned in the drug instructions.
This study identified and compared signals of ADRs associated with tenecteplase and alteplase, although tenecteplase is as effective as alteplase and has advantages such as ease of use and affordability, it cannot replace alteplase in the treatment of AIS until its safety profile is fully recognized. Additionally, previously unreported ocular ADRs and pneumonia were identified, providing valuable insights into the relationship between ADRs and the use of these thrombolytic drugs. These findings underscore the importance of continuous monitoring and effective detection of AEs to ultimately enhance the safety of AIS patients undergoing thrombolytic therapy.
本研究旨在监测、识别和比较与替奈普酶和阿替普酶相关的不良事件（AE），以探索替奈普酶用于急性缺血性卒中（AIS）的潜在安全性，并指导其使用以提高患者安全性。
为了评估真实世界数据中与替奈普酶和阿替普酶相关的AE的不成比例性，使用四种算法（ROR、PRR、BCPNN、EBGM）作为检测与两种药物相关的AE信号的指标。随后，应用Breslow-Day统计分析来比较替奈普酶和阿替普酶之间主要系统器官类别（SOC）和关键首选术语（PT）的ROR。
利用从美国食品药品监督管理局不良事件报告系统（FAERS）数据库收集的数据进行了统计分析，该数据库涵盖了2004年第一季度至2023年第一季度的19514140份病例报告。在PT水平上，有1004例报告替奈普酶为主要可疑药物（PS），并识别出2363例与替奈普酶相关的药物不良反应（ADR），阿替普酶的这两个数据分别为10945例和25266例。对27个器官系统的药物诱导ADR的发生情况进行了分析，分析揭示了一些预期的ADR，如出血、超敏反应，这与两种药物的标签一致。值得注意的是，在PT水平上，替奈普酶的“死亡”“心室颤动”“心源性休克”和“吸入性肺炎”的信号强度明显高于阿替普酶，而在PT水平上，阿替普酶的“血管性水肿”信号强度明显高于替奈普酶。此外，在PT水平上还识别出与眼部不良反应和吸入性肺炎相关的意外显著ADR，表明药物说明书中目前未提及的潜在AE。
本研究识别并比较了与替奈普酶和阿替普酶相关的ADR信号，尽管替奈普酶与阿替普酶一样有效，且具有使用方便和价格可承受等优点，但在其安全性得到充分认识之前，它不能替代阿替普酶用于AIS的治疗。此外，还识别出了以前未报告的眼部ADR和肺炎，为ADR与这些溶栓药物使用之间的关系提供了有价值的见解。这些发现强调了持续监测和有效检测AE以最终提高接受溶栓治疗的AIS患者安全性的重要性。
