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接受免疫检查点抑制剂治疗的肺癌患者的心血管不良事件:一项全国性数据库研究

Cardiovascular adverse events in patients with lung cancer treated with immune checkpoint inhibitors: a nationwide database study.

作者信息

Isawa Tsuyoshi, Togashi Shintaro, Taguri Masataka, Toi Yukihiro, Sugawara Shunichi, Toyoda Shigeru

机构信息

Department of Cardiology, Sendai Kousei Hospital, Sendai 981-0914, Japan.

Department of Nursing Care, Sendai Kousei Hospital, Sendai 981-0914, Japan.

出版信息

Oncologist. 2025 Jun 4;30(6). doi: 10.1093/oncolo/oyaf151.

Abstract

BACKGROUND

Large, diverse cohort studies are essential for determining the incidence and risk factors of major adverse cardiovascular events (MACEs) associated with immune checkpoint inhibitors (ICIs). This study aimed to (1) compare the incidence of MACEs in primary lung cancer patients receiving ICIs versus those receiving non-ICI chemotherapy, and (2) identify risk factors for MACEs in ICI-treated patients.

MATERIALS AND METHODS

We performed a retrospective analysis of primary lung cancer patients using a nationwide Japanese database. Patients were stratified by their use of ICIs, and after propensity score matching, outcomes were evaluated over 180 days.

RESULTS

The study included 743 propensity-matched patients in each cohort. The median follow-up period was 329 days (interquartile range, 147-625). At 180 days, 4.0% of ICI-treated patients experienced MACEs, significantly higher than those treated with non-ICI chemotherapy (hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.07-3.69; P-value = .030). Among MACEs, myocarditis and pericarditis occurred significantly more frequently in patients receiving ICI treatment than in those receiving non-ICI chemotherapy (P-value = .048 for both outcomes). No significant differences were observed in other MACE components. In multivariable analysis, chronic renal failure (HR, 2.16; 95% CI, 1.05-4.46; P-value = 0.038) and prior heart failure (HR, 3.08; 95% CI, 1.86-5.11; P-value < 0.001) were significant risk factors for MACEs.

CONCLUSION

ICI treatment was associated with more frequent MACEs, primarily due to myocarditis and pericarditis. Additionally, prior heart failure and chronic renal failure were key risk factors for MACEs.

CLINICAL TRIAL REGISTRATION

UMIN000051698.

摘要

背景

大型、多样化的队列研究对于确定与免疫检查点抑制剂(ICI)相关的主要不良心血管事件(MACE)的发生率和危险因素至关重要。本研究旨在:(1)比较接受ICI治疗的原发性肺癌患者与接受非ICI化疗的患者发生MACE的发生率;(2)确定接受ICI治疗患者发生MACE的危险因素。

材料与方法

我们使用日本全国性数据库对原发性肺癌患者进行了回顾性分析。根据患者是否使用ICI进行分层,并在倾向评分匹配后,对180天内的结局进行评估。

结果

每个队列中有743例倾向评分匹配的患者。中位随访期为329天(四分位间距,147 - 625天)。在180天时,接受ICI治疗的患者中有4.0%发生MACE,显著高于接受非ICI化疗的患者(风险比[HR],1.98;95%置信区间[CI],1.07 - 3.69;P值 = 0.030)。在MACE中,接受ICI治疗的患者发生心肌炎和心包炎的频率显著高于接受非ICI化疗的患者(两种结局的P值均为0.048)。在其他MACE组成部分中未观察到显著差异。在多变量分析中,慢性肾衰竭(HR,2.16;95% CI,1.05 - 4.46;P值 = 0.038)和既往心力衰竭(HR,3.08;95% CI,1.86 - 5.11;P值 < 0.001)是发生MACE的显著危险因素。

结论

ICI治疗与更频繁的MACE相关,主要原因是心肌炎和心包炎。此外,既往心力衰竭和慢性肾衰竭是发生MACE的关键危险因素。

临床试验注册

UMIN000051698。

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