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

Journal
Frontiers in pharmacology (Q1)
Published
23 July 2026
Study design
Systematic review / meta-analysis of RCTs
Evidence level
Level 1, High (CEBM 1a)
Authors
Zhe Wang, Zhiling Cheng, Yifan Zheng, Yang Liu, Zhihan Zhang, Yuan Gao, et al.
PMID
42564402
DOI
10.3389/fphar.2026.1807099

Why clinicians should know about it

  • Picked for Pharmacology (medical) (top studies of the week, 9 August 2026): High-quality evidence in a top journal
  • Picked for Epidemiology (top studies of the week, 9 August 2026).

Abstract

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.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.