Target-specific cardiotoxicity of tyrosine kinase inhibitors: a Systematic Review and meta-analysis.

OBJECTIVE: To assess the association between different tyrosine kinase inhibitors (TKIs) and the risk of major adverse cardiovascular events (MACE). DATA SOURCES: PubMed, the Cochrane Library, Embase, WanFang Data, and CNKI were searched for randomized controlled trials (RCTs) from inception to June 2026. RESULTS: A total of 25 RCTs met the inclusion criteria, encompassing 9,068 patients. The risk of MACE was significantly higher in the TKI-treated group than in the control group (odds ratio [OR] = 2.13; 95% confidence interval [CI], 1.11-4.07; P = 0.02). The ORs for QT prolongation, hypertension, and arrhythmias were 6.05 (95% CI, 3.70-9.89; P < 0.00001), 4.18 (95% CI, 2.19-7.95; P < 0.0001), and 5.40 (95% CI, 3.43-8.50; P < 0.00001), respectively. Subgroup analysis indicated that epidermal growth factor receptor inhibitors (EGFR-TKIs) were associated with the highest risk of cardiovascular adverse events, followed by vascular endothelial growth factor receptor inhibitors (VEGFR-TKIs), platelet-derived growth factor receptor inhibitors (PDGFR-TKIs), and stem cell factor receptor inhibitors (c-Kit TKIs). CONCLUSION: TKI therapy significantly prolongs progression-free survival. However, the incidence of cardiovascular adverse events, including QT prolongation, hypertension, and arrhythmias, is notably higher with TKI use. EGFR-TKIs show the highest cardiovascular risk, followed by VEGFR-TKIs, PDGFR-TKIs, and c-Kit TKIs. Clinicians should be aware of these risks and ensure regular cardiovascular monitoring during treatment. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251084805, identifier CRD420251084805.