Second-generation androgen receptor axis-targeting (ARAT) agents have become a standard treatment for patients with advanced prostate cancer (PC), however much remains unknown about the potential cardiovascular toxicities. We performed a systematic search of PubMed, Embase, Web of Science, and Cochrane library for randomized controlled trials of patients receiving ARAT agents for PC from inception to March 2023. The odds ratios (ORs) of all-grade and high-grade cardiovascular adverse events (CVAEs) for patients treated with and without ARAT agents were pooled for meta-analysis. Subgroup analyses based on PC type and treatment regimen were conducted. A total of 15 double-blind placebo-controlled phase 3 trials comprising 15,842 patients were included. In addition to hot flush and hypertension of any degree of severity, inclusion of ARAT agents was associated with a significantly higher risk of acute myocardial infarction (OR: 1.96, 95% CI: 1.05-3.68, 04), myocardial infarction (OR: 2.44, 95% CI: 1.27-4.66, 007) and angina pectoris (OR: 2.00, 95% CI: 1.00-4.02, 05). With regard to individual ARAT agents, enzalutamide was associated with a significantly higher risk of acute myocardial infarction (OR: 3.11, 95% CI: 1.17-8.28, 02), coronary artery disease (OR: 8.33, 95% CI: 1.54-44.95, 01), and high-grade hypertension (OR: 4.94, 95% CI: 1.11-22.06, 04), while abiraterone and apalutamide were associated with a significantly higher risk of angina pectoris (OR: 5.48, 95% CI: 1.23-24.33, 03) and myocardial infarction (OR: 7.00, 95% CI: 1.60-30.62, 01), respectively. The inclusion of ARAT agents was associated with a significantly higher risk of several CVAEs. Clinicians should remain vigilant, both in pre-treatment screening and monitoring for clinical symptoms and signs, when considering ARAT agent particularly for patients with pre-existing risk factors.

中文翻译：

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前列腺癌患者与雄激素受体轴靶向药物相关的心血管毒性：随机对照试验的荟萃分析

第二代雄激素受体轴靶向（ARAT）药物已成为晚期前列腺癌（PC）患者的标准治疗方法，但关于潜在的心血管毒性仍有很多未知之处。我们对 PubMed、Embase、Web of Science 和 Cochrane 图书馆进行了系统检索，查找从开始到 2023 年 3 月接受 ARAT 药物治疗 PC 的患者的随机对照试验。所有级别和高级心血管不良反应的比值比 (OR)汇总使用和未使用 ARAT 药物治疗的患者的事件 (CVAE) 进行荟萃分析。根据 PC 类型和治疗方案进行亚组分析。总共纳入了 15 项双盲安慰剂对照 3 期试验，涉及 15,842 名患者。除了任何严重程度的潮热和高血压之外，ARAT 药物的加入与急性心肌梗死（OR：1.96，95% CI：1.05-3.68，04）、心肌梗死（OR：2.44）的风险显着升高相关。 , 95% CI: 1.27-4.66, 007) 和心绞痛 (OR: 2.00, 95% CI: 1.00-4.02, 05)。对于个别 ARAT 药物，恩杂鲁胺与急性心肌梗死（OR：3.11，95% CI：1.17-8.28，02）、冠状动脉疾病（OR：8.33，95% CI：1.54-44.95）的风险显着升高相关。 , 01) 和高度高血压 (OR: 4.94, 95% CI: 1.11-22.06, 04)，而阿比特龙和阿帕鲁胺与显着较高的心绞痛风险相关 (OR: 5.48, 95% CI: 1.23- 24.33, 03) 和心肌梗死 (OR: 7.00, 95% CI: 1.60-30.62, 01)。 ARAT 药物的加入与多种 CVAE 的风险显着升高相关。临床医生在考虑使用 ARAT 药物时，尤其是对于已有危险因素的患者，在治疗前筛查和临床症状和体征监测方面应保持警惕。