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接受免疫检查点抑制剂治疗患者的新诊断心血管疾病:对一家学术性三级医疗中心患者的回顾性分析

Newly diagnosed cardiovascular disease in patients treated with immune checkpoint inhibitors: a retrospective analysis of patients at an academic tertiary care center.

作者信息

Waheed Nida, Fradley Michael G, DeRemer David L, Mahmoud Ahmad, Shah Chintan P, Langaee Taimour Y, Lipori Gloria P, March Keith, Pepine Carl J, Cooper-DeHoff Rhonda M, Wu Yonghui, Gong Yan

机构信息

Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.

Cardio-Oncology Center of Excellence, Division of Cardiology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

出版信息

Cardiooncology. 2021 Mar 18;7(1):10. doi: 10.1186/s40959-021-00097-9.

Abstract

BACKGROUND

Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of newly diagnosed cardiovascular disease in patients treated with ICIs at a large, tertiary care center.

METHODS

All patients with a cancer diagnosis who received any ICI treatment in the University of Florida's Integrated Data Repository from 2011 to 2017 were included. Cardiovascular disease was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment.

RESULTS

Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one new cardiovascular disease after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Incident cardiovascular disease was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in ICI treated patients with a concomitant diagnosis of incident cardiovascular disease was higher compared to those who did not (66.1% vs. 41.4%, odds ratio = 2.77, 1.55-4.95, p = 0.0006).

CONCLUSIONS

This study suggests a high incidence of newly diagnosed cardiovascular disease after the initiation of ICI therapy in a real-world clinical setting.

摘要

背景

免疫检查点抑制剂(ICIs)是一类新型抗癌药物,已在实体瘤和血液系统恶性肿瘤中显示出临床疗效。ICIs与包括心脏毒性在内的免疫相关不良事件的发生有关。我们在一家大型三级医疗中心估计了接受ICIs治疗的患者中新诊断心血管疾病的发生率。

方法

纳入2011年至2017年在佛罗里达大学综合数据存储库中接受任何ICI治疗的所有癌症诊断患者。心血管疾病定义为ICI治疗开始后新出现的心肌病、心力衰竭、心律失常、心脏传导阻滞、心包疾病或心肌炎的ICD诊断代码。

结果

在102,701例恶性肿瘤诊断患者中,424例接受了至少一种ICI。62例(14.6%)患者在ICI治疗开始后被诊断出至少一种新的心血管疾病。在接受一种ICI的374例患者中,21例(5.6%)发生心力衰竭。在依次接受两种ICI的49例患者中,3例(6.1%)发生心力衰竭和/或心肌病。首次接触ICI后中位63天诊断出心血管疾病。1例患者在接受纳武单抗28天后发生心肌炎。与未合并心血管疾病的ICI治疗患者相比,合并心血管疾病的ICI治疗患者死亡率更高(66.1%对41.4%,优势比=2.77,1.55 - 4.95,p = 0.0006)。

结论

本研究表明,在真实世界临床环境中,ICI治疗开始后新诊断心血管疾病的发生率较高。

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