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

Zhe Wang1,2, Zhiling Cheng1,2, Yifan Zheng1,2

  • 1Department of Pharmacy, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, China.

Frontiers in Pharmacology
|August 7, 2026
PubMed
Abstract

Insights

Tyrosine kinase inhibitors (TKIs) increase the risk of major adverse cardiovascular events (MACE), including QT prolongation, hypertension, and arrhythmias. Epidermal growth factor receptor inhibitors (EGFR-TKIs) pose the highest cardiovascular risk among TKIs.

Area of Science:

  • Cardiology
  • Oncology
  • Pharmacology

Background:

  • Tyrosine kinase inhibitors (TKIs) are crucial in cancer therapy, improving progression-free survival.
  • However, TKIs are associated with significant cardiovascular adverse events.
  • Understanding these risks is vital for patient management.

Purpose of the Study:

  • To evaluate the association between various tyrosine kinase inhibitors (TKIs) and the risk of major adverse cardiovascular events (MACE).
  • To identify specific TKI subclasses with higher cardiovascular risks.

Main Methods:

  • A systematic review and meta-analysis of 25 randomized controlled trials (RCTs) involving 9,068 patients.
  • Searched major databases including PubMed, Cochrane Library, and Embase up to June 2026.
  • Analyzed the incidence of MACE and specific cardiovascular events like QT prolongation, hypertension, and arrhythmias.

Main Results:

  • TKI therapy significantly increased the risk of MACE (OR = 2.13; P = 0.02).
  • Elevated risks observed for QT prolongation (OR = 6.05), hypertension (OR = 4.18), and arrhythmias (OR = 5.40).
  • Epidermal growth factor receptor inhibitors (EGFR-TKIs) demonstrated the highest cardiovascular risk, followed by VEGFR-TKIs, PDGFR-TKIs, and c-Kit TKIs.

Conclusions:

  • TKI treatment is linked to a substantially higher incidence of cardiovascular adverse events.
  • EGFR-TKIs present the greatest cardiovascular risk, necessitating careful monitoring.
  • Clinicians must proactively monitor cardiovascular health in patients receiving TKI therapy.
Keywords:
TKIscardiovascular adverse eventsmajor adverse cardiovascular eventsmeta-analysistarget

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