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<p>Major adverse cardiovascular events (MACE) in patients with liver cancer receiving vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKI) remain uncertain. This retrospective cohort study aimed to evaluate the association between VEGF-TKIs and MACE and develop a risk prediction score. Using the Taiwan Cancer Registry linked with the Taiwan National Insurance Claim Database, 11,960 VEGF-TKI users were matched to 11,960 non-users by age and sex. Cause-specific hazard ratios (HRs) were estimated using multivariable Cox models with competing risk of non-cardiovascular death; propensity score (PS)-adjusted or PS-matched models were additionally conducted. During follow-up, the incidence of MACE was 49.5 versus 28.3 per 1,000 person-years in VEGF-TKI users and non-users. VEGF-TKI use was associated with increased MACE risk in multivariable analysis (adjusted HR 1.31; 95% CI 1.14–1.50); however, PS-adjusted and PS-matched models show non-significant associations. Because proportional hazards assumptions were violated, a 60-day landmark analysis was conducted, in which the increased risk was again significant across analytic approaches, including multivariable adjusted (HR 1.92; 95% CI 1.63–2.27), PS-adjusted (HR 1.35; 95% CI 1.00-1.82) and PS-matched models (HR 1.30; 95% CI 1.03–1.63). A point-based score was developed using a multivariable sub-distribution hazard model and assessed by a time-dependent c-index. The score demonstrated good discrimination with c-indices of 79.9% (3 months) and 74.2% (6 months). VEGF-TKIs were associated with increased risk of MACE among liver cancer patients. Landmark analyses indicated a persistently elevated risk among patients surviving beyond early treatment. A risk score based on prior cardiovascular history may help identify high-risk patients.</p> Graphical Abstract <p></p>

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Cardiovascular Risk and Prediction Model of Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitors in Patients with Liver Cancer

  • 期刊论文

  • 发表日期：

    2026年2月17日

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  • Yen-Chou Chen,
  • Chun-Yao Huang,
  • Li-Ming Lien,
  • Jin-Hua Chen,
  • Bagas Suryo Bintoro,
  • Fang-I Hsieh

摘要

Major adverse cardiovascular events (MACE) in patients with liver cancer receiving vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKI) remain uncertain. This retrospective cohort study aimed to evaluate the association between VEGF-TKIs and MACE and develop a risk prediction score. Using the Taiwan Cancer Registry linked with the Taiwan National Insurance Claim Database, 11,960 VEGF-TKI users were matched to 11,960 non-users by age and sex. Cause-specific hazard ratios (HRs) were estimated using multivariable Cox models with competing risk of non-cardiovascular death; propensity score (PS)-adjusted or PS-matched models were additionally conducted. During follow-up, the incidence of MACE was 49.5 versus 28.3 per 1,000 person-years in VEGF-TKI users and non-users. VEGF-TKI use was associated with increased MACE risk in multivariable analysis (adjusted HR 1.31; 95% CI 1.14–1.50); however, PS-adjusted and PS-matched models show non-significant associations. Because proportional hazards assumptions were violated, a 60-day landmark analysis was conducted, in which the increased risk was again significant across analytic approaches, including multivariable adjusted (HR 1.92; 95% CI 1.63–2.27), PS-adjusted (HR 1.35; 95% CI 1.00-1.82) and PS-matched models (HR 1.30; 95% CI 1.03–1.63). A point-based score was developed using a multivariable sub-distribution hazard model and assessed by a time-dependent c-index. The score demonstrated good discrimination with c-indices of 79.9% (3 months) and 74.2% (6 months). VEGF-TKIs were associated with increased risk of MACE among liver cancer patients. Landmark analyses indicated a persistently elevated risk among patients surviving beyond early treatment. A risk score based on prior cardiovascular history may help identify high-risk patients.

Graphical Abstract