Adverse Cardiovascular Events Associated With Cyclin-Dependent Kinase 4/6 Inhibitors in Patients With Metastatic Breast Cancer.
Adverse Cardiovascular Events Associated With Cyclin-Dependent Kinase 4/6 Inhibitors in Patients With Metastatic Breast Cancer.
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DOI：
10.1161/jaha.123.029361
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发表时间：
2023-06-20
影响因子：
5.4
通讯作者：
Gong, Yan
中科院分区：
文献类型：
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作者：
Fradley, Michael G.;Nguyen, Nam H. K.;Madnick, David;Chen, Yiqing;DeMichele, Angela;Makhlin, Igor;Dent, Susan;Lefebvre, Benedicte;Carver, Joseph;Upshaw, Jenica N.;DeRemer, David;Ky, Bonnie;Guha, Avirup;Gong, Yan
细胞周期蛋白依赖性激酶（CDK）4和6抑制剂可显著改善激素受体阳性转移性乳腺癌患者的生存期。关于这些治疗的心血管不良事件（CVAE）的流行病学数据很少。使用OneFlorida Data Trust，将既往无心血管疾病且接受至少1种CDK 4/6抑制剂的成人患者纳入分析。从国际疾病分类第九版和第十版（ICD-9/10）代码中识别的CVAE包括高血压、房颤（AF）/房扑（AFL）、心力衰竭/心肌病、缺血性心脏病和心包疾病。使用竞争风险分析（Fine-Gray模型）确定CDK 4/6抑制剂治疗与CVAE事件之间的相关性。使用考克斯比例风险模型研究CVAE对全因死亡的影响。进行倾向权重分析，以比较这些患者与接受蒽环类药物治疗的患者队列。共有1376例接受CDK 4/6抑制剂治疗的患者纳入分析。CVAE发生率为24%（35.9/100人-年）。与蒽环类药物相比，接受CKD 4/6抑制剂治疗的患者的CVAE略高（P=0.063），CDK 4/6组中与AF/AFL或心肌病/心力衰竭发展相关的死亡率较高。心肌病/心力衰竭和AF/AFL的发生与全因死亡增加相关（校正风险比[HR]分别为4.89 [95% CI，2.98-8.05]和5.88 [95% CI，3.56-9.73]）。CVAE在CDK 4/6抑制剂中可能比以前认识到的更常见，在这些发生AF/AFL或心力衰竭的患者中死亡率增加。需要进一步的研究来明确确定与这些新型抗癌治疗相关的心血管风险。
Cyclin‐dependent kinase (CDK) 4 and 6 inhibitors have significantly improved survival in patients with hormone receptor–positive metastatic breast cancer. There are few data regarding the epidemiology of cardiovascular adverse events (CVAEs) with these therapies. Using the OneFlorida Data Trust, adult patients without prior cardiovascular disease who received at least 1 CDK4/6 inhibitor were included in the analysis. CVAEs identified from International Classification of Diseases, Ninth and Tenth Revisions (ICD‐9/10) codes included hypertension, atrial fibrillation(AF)/atrial flutter (AFL), heart failure/cardiomyopathy, ischemic heart disease, and pericardial disease. Competing risk analysis (Fine–Gray model) was used to determine the association between CDK4/6 inhibitor therapy and incident CVAEs. The effect of CVAEs on all‐cause death was studied using Cox proportional hazard models. Propensity‐weight analyses were performed to compare these patients to a cohort of patients treated with anthracyclines. A total of 1376 patients treated with CDK4/6 inhibitors were included in the analysis. CVAEs occurred in 24% (35.9 per 100 person‐years). CVAEs were slightly higher in patients who received CKD4/6 inhibitors compared with anthracyclines (P=0.063), with higher death rate associated with the development of AF/AFL or cardiomyopathy/heart failure in the CDK4/6 group. The development of cardiomyopathy/heart failure and AF/AFL was associated with increased all‐cause death (adjusted hazard ratio [HR], 4.89 [95% CI, 2.98–8.05]; and 5.88 [95% CI, 3.56–9.73], respectively). CVAEs may be more common with CDK4/6 inhibitors than previously recognized, with increased death rates in these patients who develop AF/AFL or heart failure. Further research is needed to definitively determine cardiovascular risk associated with these novel anticancer treatments.