Kattan Lana A, Abulola Sara M, Mohamed Ibrahim Mohamed Izham, Maayah Zaid H
Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, 2713, Doha, Qatar.
Clinical Pharmacy and Practice Department, College of Pharmacy, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar.
Cardiovasc Toxicol. 2025 May;25(5):692-718. doi: 10.1007/s12012-025-09986-2. Epub 2025 Apr 3.
Anthracyclines are effective antineoplastic drugs; however, their use is constrained by dose-dependent cardiotoxicity. Vascular endothelial dysfunction is an early independent event in cardiovascular diseases and may precede anthracycline-induced cardiotoxicity. Brachial flow-mediated dilation (FMD) is a non-invasive technique for evaluating vascular endothelial function. We evaluated the evidence on anthracycline-induced vascular endothelial dysfunction in cancer patients and survivors using FMD. Studies measuring FMD in anthracycline-treated active cancer patients or survivors were retrieved from inception to August 2024 using PubMed, Embase, and Scopus. The primary outcome was the difference in FMD between anthracycline-treated patients and healthy controls or baseline. We performed the meta-analysis using a random-effects model and evaluated the certainty in effect estimates. Overall, 18 studies (n = 841 patients) met the inclusion criteria. Compared to the baseline, a non-significant change toward a decline in FMD was observed. However, a significant reduction in FMD was observed in anthracycline-treated patients compared to healthy controls (standardized mean difference (SMD): - 0.6082; 95% CI: - 0.8963 to - 0.3201; p < 0.0001). Subgroup analyses revealed consistent significant reductions in FMD for childhood cancers (SMD: - 0.7189; 95% CI: - 0.9903 to - 0.4476; p < 0.0001), while adult cancers showed no significant difference. No significant publication bias was detected overall for healthy control comparisons. High heterogeneity was observed in the included studies (I = 81.7808% versus healthy controls and I = 75.6876% for childhood cancers subgroup analysis). Anthracyclines induce vascular endothelial dysfunction, indicated by lower FMD in cancer patients and survivors, particularly among those with childhood cancers, who might be at risk of long-term cardiovascular complications.
蒽环类药物是有效的抗肿瘤药物；然而，它们的使用受到剂量依赖性心脏毒性的限制。血管内皮功能障碍是心血管疾病早期的独立事件，可能先于蒽环类药物引起的心脏毒性。肱动脉血流介导的血管舒张（FMD）是一种评估血管内皮功能的非侵入性技术。我们使用FMD评估了癌症患者和幸存者中蒽环类药物引起的血管内皮功能障碍的证据。通过PubMed、Embase和Scopus检索了从开始到2024年8月测量接受蒽环类药物治疗的现役癌症患者或幸存者FMD的研究。主要结局是接受蒽环类药物治疗的患者与健康对照或基线之间FMD的差异。我们使用随机效应模型进行荟萃分析，并评估效应估计的确定性。总体而言，18项研究（n = 841例患者）符合纳入标准。与基线相比，观察到FMD有向下降的非显著变化。然而，与健康对照相比，接受蒽环类药物治疗的患者FMD显著降低（标准化平均差（SMD）：-0.6082；95%CI：-0.8963至-0.3201；p < 0.0001）。亚组分析显示，儿童癌症患者的FMD持续显著降低（SMD：-0.7189；95%CI：-0.9903至-0.4476；p < 0.0001），而成人癌症患者则无显著差异。总体而言，在与健康对照的比较中未检测到显著的发表偏倚。纳入的研究中观察到高度异质性（与健康对照相比I = 81.7808%，儿童癌症亚组分析I = 75.6876%）。蒽环类药物会导致血管内皮功能障碍，癌症患者和幸存者的FMD较低表明了这一点，尤其是儿童癌症患者，他们可能有长期心血管并发症的风险。
