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Updated: Oct 9, 2025
Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment
Published on: January 7, 2015
Major adverse cardiovascular events associated with VEGF-targeted anticancer tyrosine kinase inhibitors: a real-life
P Vallerio1, A Orenti2, F Tosi3
1De Gasperis Cardio Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
Background:
Vascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment and burdened by cardiovascular toxicity. The majority of data come from clinical trials, thus in selected populations. The aim of our study is to evaluate the cardiotoxicity profile of VEGFR-targeted TKIs and the impact of cardiovascular risk factors in a real-life population.
Patients And Methods:
In this cohort, population-based study, patients treated with VEGFR-targeted TKIs, bevacizumab and trastuzumab between 2009 and 2014 were analyzed. A multi-source strategy for data retrieval through hospital, pharmaceutical and administrative databases of the Lombardy region, Italy, has been adopted. The primary endpoint was to determine the incidence and type of major adverse cardiovascular events (MACEs) along with their temporal trend. The secondary endpoint was to define the impact of cardiovascular risk factors in the occurrence of MACEs.
Results:
A total of 829 patients were treated with VEGFR-targeted TKIs. Eighty-one MACEs occurred in the first year of follow-up [crude cumulative incidence (CCI): 9.79%] mainly consisting of arterial thrombotic events (ATEs, 31 events, CCI: 3.99%), followed by rhythm disorders (22 events, CCI: 2.66%), pulmonary embolisms and heart failures (13 events each, CCI: 1.57%). While the incidence of most MACEs showed a plateau after 6 months, ATEs kept increasing along the year of follow-up. Hypertension and dyslipidemia were associated with an increase in risk of ATEs [relative risk difference (RRD) +209.8% and +156.2%, respectively], while the presence of previous MACEs correlated with a higher risk of all MACEs in multivariate analysis (RRD 151.1%, 95% confidence interval 53.6% to 310.3%, P < 0.001).
Conclusions:
MACEs occur in a clinically significant proportion of patients treated with VEGFR-targeted TKIs, with ATEs being predominant, mainly associated with hypertension and dyslipidemia. A clinical algorithm for effective proactive management of these patients is warranted.
Insights
Vascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors (TKIs) cause significant cardiovascular toxicity, with arterial thrombotic events (ATEs) being predominant. Hypertension and dyslipidemia increase ATE risk, necessitating proactive patient management.
Area of Science:
- Cardiology
- Oncology
- Pharmacology
Background:
- Vascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors (TKIs) are crucial in cancer therapy but are associated with cardiovascular toxicity.
- Existing data on VEGFR-TKI cardiotoxicity primarily stem from clinical trials involving selected patient populations.
- Real-world data are needed to understand the cardiotoxicity profile and the influence of cardiovascular risk factors in broader patient groups.
Purpose of the Study:
- To evaluate the cardiotoxicity profile of VEGFR-targeted TKIs in a real-life population.
- To determine the incidence, types, and temporal trends of major adverse cardiovascular events (MACEs) associated with VEGFR-TKIs.
- To assess the impact of pre-existing cardiovascular risk factors on the occurrence of MACEs.
Main Methods:
- A retrospective cohort study analyzing 829 patients treated with VEGFR-targeted TKIs (bevacizumab, trastuzumab) between 2009 and 2014.
- Data were retrieved from multiple sources, including hospital, pharmaceutical, and administrative databases in the Lombardy region, Italy.
- Primary endpoint: incidence and temporal trend of MACEs; Secondary endpoint: impact of cardiovascular risk factors on MACEs.
Main Results:
- Eighty-one MACEs occurred within the first year, with a crude cumulative incidence of 9.79%.
- Arterial thrombotic events (ATEs) were the most frequent MACEs (3.99%), followed by rhythm disorders (2.66%), pulmonary embolism, and heart failure (1.57% each).
- Hypertension and dyslipidemia significantly increased the risk of ATEs, while prior MACEs correlated with a higher overall MACE risk.
Conclusions:
- VEGFR-targeted TKIs are associated with a significant incidence of MACEs, particularly ATEs, in real-world clinical practice.
- Cardiovascular risk factors such as hypertension and dyslipidemia are key contributors to VEGFR-TKI-related ATEs.
- A proactive clinical management strategy is essential for patients receiving VEGFR-targeted TKIs to mitigate cardiovascular risks.
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