阿特唑单抗和贝伐单抗联合用药的心血管毒性评价

T. Niimura, M. Goda, Koji Miyata, J. Matsumoto, T. Yoshioka, H. Hamano, F. Aizawa, Kenta Yagi, Y. Izawa-Ishizawa, Y. Zamami, K. Ishizawa
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摘要

免疫检查点抑制剂(ICI) atezolizumab和血管内皮生长因子(VEGF)抑制剂贝伐单抗(bevacizumab)的联合治疗是肝细胞癌全身治疗的首选。已知免疫相关的心血管毒性-心肌炎和心包炎-在ICI治疗期间发生。相反,VEGF抑制剂(vegfi)会引起心血管并发症,如高血压和心力衰竭。因此,已经认识到ICIs和vegfi具有不同的心血管毒性,但它们联合使用的影响尚不清楚。在这里,我们的目的是利用世界卫生组织不良事件报告数据库- vigibase来研究atezolizumab与贝伐单抗联合使用的心血管毒性。方法:我们分析了截至2022年12月的VigiBase数据。为了评估与阿特唑单抗、贝伐单抗及其联合治疗21例不良事件相关的报告频率,我们计算了报告的优势比和信息成分。分析了与每种药物使用相关的各种心血管毒性的致死率。结果:该数据库分别包括84,951、10,595和2,092份贝伐单抗、阿特唑单抗及其联合治疗的报告。检测阿特唑单抗与贝伐单抗联合用药组高血压、动脉栓塞及血栓形成、室上性心动过速、心力衰竭、心肌炎、出血相关临床事件、静脉栓塞及血栓形成、心肌病、呼吸衰竭的不比例信号。用阿特唑单抗或贝伐单抗单独治疗也可以检测到这些不良事件的信号。与阿特唑单抗(6.19%)和贝伐单抗(4.54%)相比,两种药物联合用药的静脉栓塞和血栓致死率最高(12.82%)。讨论:由于阿特唑单抗和贝伐单抗联合使用,心血管毒性与单独使用类似,没有观察到新的安全性问题。两种药物联合使用时应谨慎,因为联合治疗会增加血栓栓塞的死亡率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Evaluation of cardiovascular toxicity of the atezolizumab and bevacizumab combination
Introduction: The combination of atezolizumab, an immune checkpoint inhibitor (ICI), and bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, is the first choice for systemic therapy in hepatocellular carcinoma. Immune-related cardiovascular toxicity—myocarditis and pericarditis—are known to occur during ICI treatment. By contrast, VEGF inhibitors (VEGFIs) cause cardiovascular complications such as hypertension and heart failure. Thus, different cardiovascular toxicities have been recognized for ICIs and VEGFIs, but the impact of their combination remains unclear. Here, we aimed to investigate the cardiovascular toxicity profile of atezolizumab in combination with bevacizumab using the World Health Organization adverse event reporting database—VigiBase.Methods: We analyzed data included in VigiBase till December 2022. To evaluate the frequency of reports related to atezolizumab, bevacizumab, and their combinations for 21 adverse events, we calculated the reporting odds ratio and information component. Analyses of the fatality of various cardiovascular toxicities associated with the use of each drug were performed.Results: The database included 84,951, 10,595, and 2,092 reports of treatment with bevacizumab, atezolizumab, and their combination, respectively. The disproportionality signal of hypertension, arterial embolism and thrombosis, supraventricular tachyarrhythmias, heart failure, myocarditis, hemorrhage-related clinical events, venous embolism and thrombosis, cardiomyopathy, respiratory failure with combination regimen of atezolizumab and bevacizumab was detected. Signals of these adverse events were also detected treatment with either atezolizumab or bevacizumab alone. Venous embolism and thrombosis exhibited the highest fatality rate in the two drug combination (12.82%) relative to those of atezolizumab (6.19%) and bevacizumab (4.54%).Discussion: Cardiovascular toxicity, owing to the combination of atezolizumab and bevacizumab, was similar to that of each single agent, and no new safety concerns were observed. Caution should be exercised when combining the two drugs since the fatality rate of thromboembolism increases with combination treatment.
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