文章：

CDK4/6抑制剂心血管毒性特征分析：一项真实世界药物警戒研究

Profiling the Cardiovascular Toxicities of CDK4/6 Inhibitors: A Real-World Pharmacovigilance Study

原文发布日期：17 August 2024

DOI: 10.3390/cancers16162869

类型: Article

开放获取: 是

英文摘要：

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are approved for the treatment of human epidermal growth factor receptor 2 (HER-2)-negative, hormone receptor-positive breast cancer. The cardiovascular toxicity of CDK4/6 inhibitors is not well understood. This study aims to profile the cardiac events associated with CDK4/6 inhibitors. Reports from 2015Q1 to 2024Q1 were obtained from the FDA Adverse Event Reporting System (FAERS). Reports identifying palbociclib, ribociclib, and abemaciclib as the primary suspect were examined for cardiovascular toxicity, including hypertension, cardiac failure, cardiomyopathy, arrhythmia, myocardial infarction, and myocarditis. Signal detection was performed using the proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). A total of 69,139 reports were analyzed. The median time to adverse events was 69 days (interquartile range [IQR], 18–260 days). Of these, 2065 reports documented cardiac adverse events. Ribociclib and QT prolongation were re-confirmed as a signal (PRR 8.43, ROR 8.65, IC025 2.86). Hypertension and cardiac failure were the most frequently reported cardiovascular toxicities. This study demonstrates that the use of CDK4/6 inhibitors is associated with cardiovascular adverse events, such as heart failure and hypertension. Further research is needed to understand the mechanisms and risk factors contributing to the cardiovascular toxicity of CDK4/6 inhibitors.

摘要翻译： 

细胞周期蛋白依赖性激酶4和6（CDK4/6）抑制剂已被批准用于治疗人表皮生长因子受体2（HER-2）阴性、激素受体阳性乳腺癌。目前对CDK4/6抑制剂心血管毒性的认识尚不充分。本研究旨在分析CDK4/6抑制剂相关的心脏不良事件。研究数据提取自美国食品药品监督管理局不良事件报告系统（FAERS）2015年第一季度至2024年第一季度的报告，筛选出以帕博西利、瑞博西利和阿贝西利为主要怀疑药物的报告，重点分析其心血管毒性表现，包括高血压、心力衰竭、心肌病、心律失常、心肌梗死和心肌炎。采用比例报告比（PRR）、报告比值比（ROR）和信息成分（IC）进行信号检测。共分析69,139份报告，不良事件发生中位时间为69天（四分位距[IQR]为18-260天）。其中2065份报告记录了心脏不良事件。瑞博西利与QT间期延长的关联性再次被确认为显著信号（PRR 8.43，ROR 8.65，IC025 2.86）。高血压和心力衰竭是最常见的心血管毒性反应。本研究表明，使用CDK4/6抑制剂与心力衰竭、高血压等心血管不良事件存在关联，需进一步研究其毒性机制及风险因素。

原文链接：

Profiling the Cardiovascular Toxicities of CDK4/6 Inhibitors: A Real-World Pharmacovigilance Study