Chiang Cho-Han, Song Junmin, Chi Kuan-Yu, Chang Yu-Cheng, Xanthavanij Nutchapon, Chang Yu, Hsia Yuan Ping, Chiang Cho-Hung, Ghamari Azin, Reynolds Kerry L, Lin Shuwen, Xu Xiaocao Haze, Neilan Tomas G
Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, MA, USA.
Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Eur J Cancer. 2025 Feb 5;216:115170. doi: 10.1016/j.ejca.2024.115170. Epub 2024 Dec 11.
Immune checkpoint inhibitors (ICIs) are associated with an increased risk of major adverse cardiovascular events (MACE). Glucagon-like peptide-1 agonists (GLP1a), initially developed for type 2 diabetes mellitus (T2DM), have shown promising results in reducing cardiovascular events. We aimed to investigate the effect of GLP1a on cardiovascular events in patients receiving ICIs.
We conducted a retrospective, propensity score-matched cohort study using the TriNetX database. We identified adults with cancer and T2DM who received ICIs between April 2013 and May 2023. The primary efficacy outcome was incident MACE, defined as a composite of myocardial infarction, need for coronary revascularization, heart failure, ischemic stroke, and cardiac arrest. The secondary efficacy outcomes were the individual components of MACE as well as myocarditis and pericarditis. Safety outcomes included the occurrence of immune-related adverse events, serious adverse events related to GLP1a use, and all-cause mortality.
We identified 7651 patients eligible for inclusion, among which 479 received GLP1a and 7172 received non-GLP1a diabetes medications. After matching (469 patients each), baseline characteristics were well-balanced. Over a median 12-month follow-up, the GLP1a cohort had a significantly lower MACE incidence than the non-GLP1a cohort (9.0 vs. 17.1 events per 100 patient-years) with a 54 % lower risk of MACE (Hazard ratio (HR),0.46 [95 % CI: 0.32-0.67]). There were reductions in myocardial infarction or need for coronary revascularization, heart failure, and all-cause mortality, with no differences in other cardiovascular events. GLP1a use did not increase risk of adverse events, including pancreatitis, biliary disease, bowel obstruction, gastroparesis, and immune-related adverse events.
GLP1a use in cancer patients with T2DM receiving ICIs was associated with reduced MACE and all-cause mortality without an increased risk in serious adverse events.
免疫检查点抑制剂（ICI）与主要不良心血管事件（MACE）风险增加相关。最初用于2型糖尿病（T2DM）治疗的胰高血糖素样肽-1激动剂（GLP1a）在降低心血管事件方面已显示出有前景的结果。我们旨在研究GLP1a对接受ICI治疗患者心血管事件的影响。
我们使用TriNetX数据库进行了一项回顾性、倾向评分匹配队列研究。我们纳入了2013年4月至2023年5月期间接受ICI治疗的成年癌症患者和T2DM患者。主要疗效结局为发生MACE，定义为心肌梗死、冠状动脉血运重建需求、心力衰竭、缺血性中风和心脏骤停的综合情况。次要疗效结局为MACE的各个组成部分以及心肌炎和心包炎。安全性结局包括免疫相关不良事件的发生、与使用GLP1a相关的严重不良事件以及全因死亡率。
我们确定了7651名符合纳入标准的患者，其中479名接受GLP1a治疗，7172名接受非GLP1a糖尿病药物治疗。匹配后（每组469名患者），基线特征达到良好平衡。在中位12个月的随访期内，GLP1a队列的MACE发生率显著低于非GLP1a队列（每100患者年9.0次事件对17.1次事件），MACE风险降低54%（风险比（HR），0.46 [95%置信区间：0.32 - 0.67]）。心肌梗死或冠状动脉血运重建需求、心力衰竭和全因死亡率均有所降低，其他心血管事件无差异。使用GLP1a并未增加不良事件风险，包括胰腺炎、胆道疾病、肠梗阻、胃轻瘫和免疫相关不良事件。
在接受ICI治疗的T2DM癌症患者中使用GLP1a与MACE和全因死亡率降低相关，且严重不良事件风险未增加。
