Anthracyclines-Induced Vascular Endothelial Dysfunction in Cancer Patients and Survivors Using Brachial Flow-Mediated Dilation (FMD) Tool: A Systematic Review and Meta-Analysis

Abstract

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 (I2 = 81.7808% versus healthy controls and I2 = 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.