随着细胞毒性T淋巴细胞相关蛋白4（CTLA-4）抑制剂的出现，恶性肿瘤患者的预后显着改善。然而，心血管不良事件的发生率也有所增加，这会影响肿瘤的治疗。在这项研究中，我们通过分析涉及 CTLA-4 抑制剂治疗的已报道试验，评估了 CTLA-4 抑制剂引起的不良心血管事件的发生率和严重程度。2013 年 1 月 1 日至 2022 年 11 月 30 日以英文发表的随机临床试验，使用 Cochrane 图书馆和 PubMed 数据库进行检索。所有纳入的试验均检查了所有级别和 3-5 级心脏和血管不良事件。这些涉及 CTLA-4 抑制剂与安慰剂、CTLA-4 抑制剂加化疗与单独化疗的比较、CTLA-4 抑制剂联合 PD-1/PD-L1 抑制剂与单独 PD-1/PD-L1 抑制剂的比较以及 CTLA-4抑制剂加靶剂 PD-1/PD-L1 抑制剂加靶剂。使用 Mantel-Haenszel 方法计算比值比 (OR) 和相应的 95% 置信区间 (CI)。总共纳入了 20 项试验。 CTLA-4抑制剂显着增加所有级别心血管毒性的发生率（OR = 1.33，95% CI：1.00-1.75，p = 0.05）。接受单药CTLA-4抑制剂治疗的恶性肿瘤患者所有级别心血管毒性的发生率均升高（OR = 1.73，95% CI：1.13-2.65，p = 0.01），以及3-3级的发生率5 项心血管不良事件（OR = 2.00，95% CI：1.08-3.70，p = 0.03）。与非CTLA-4抑制剂组相比，CTLA-4抑制剂联合化疗、PD-1/PD-L1抑制剂或靶向药物对心脏和血管毒性的发生率没有显着影响。暴露于CTLA-4抑制剂的患者中，3-5级心力衰竭、高血压、心包积液、心肌炎和心房颤动的发生率明显较高，但数据无统计学意义。我们的研究结果表明，所有心血管疾病的发生率服用 CTLA-4 抑制剂的患者的毒性和严重心血管毒性增加。此外，严重心血管毒性事件的风险与不良事件的类型无关。根据这些结果，医生应评估 CTLA-4 抑制剂在治疗恶性肿瘤时的益处和风险。© 2024 作者。约翰·威利 (John Wiley) 出版的《癌症创新》

With the emergence of cytotoxic T lymphocyte-associated protein-4 (CTLA-4) inhibitors, the outcomes of patients with malignant tumors have improved significantly. However, the incidence of cardiovascular adverse events has also increased, which can affect tumor treatment. In this study, we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA-4 inhibitors by analyzing reported trials that involved CTLA-4 inhibitor therapy.Randomized clinical trials published in English from January 1, 2013, to November 30, 2022, were searched using the Cochrane Library and PubMed databases. All included trials examined all grade and grades 3-5 cardiac and vascular adverse events. These involved comparisons of CTLA-4 inhibitors to placebo, CTLA-4 inhibitors plus chemotherapy to chemotherapy alone, CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors to PD-1/PD-L1 inhibitors alone, and CTLA-4 inhibitors plus target agent to PD-1/PD-L1 inhibitors plus target agent. The odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method.Overall, 20 trials were included. CTLA-4 inhibitors significantly increased the incidence of all-grade cardiovascular toxicity (OR = 1.33, 95% CI: 1.00-1.75, p = 0.05). The incidence of all-grade cardiovascular toxicity increased in malignant tumor patients who received single-agent CTLA-4 inhibitors (OR = 1.73, 95% CI: 1.13-2.65, p = 0.01), as well as the incidence rate of grades 3-5 cardiovascular adverse events (OR = 2.00, 95% CI: 1.08-3.70, p = 0.03). Compared with the non-CTLA-4 inhibitor group, CTLA-4 inhibitors plus chemotherapy, PD-1/PD-L1 inhibitors, or target agent did not significantly affect the incidence of cardiac and vascular toxicity. The incidence of grades 3-5 cardiac failure, hypertension, pericardial effusion, myocarditis, and atrial fibrillation were much higher among patients exposed to CTLA-4 inhibitor, but the data were not statistically significant.Our findings suggest that the incidence rate of all cardiovascular toxicity and severe cardiovascular toxicity increased in patients who were administered CTLA-4 inhibitors. In addition, the risk of serious cardiovascular toxic events was independent of the type of adverse event. From these results, physicians should assess the benefits and risks of CTLA-4 inhibitors when treating malignancies.© 2024 The Authors. Cancer Innovation published by John Wiley & Sons Ltd on behalf of Tsinghua University Press.