Risk of Thromboembolic Events and Major Adverse Cardiovascular Events Following Antivascular Endothelial Growth Factor Therapy in Patients with Colorectal Cancer

Abstract

Antivascular endothelial growth factor (anti-VEGF) therapy has been a standard treatment for patients with metastatic colorectal cancer. However, the risk of thromboembolic events and cardiovascular events associated with this therapy remains controversial. We assessed whether anti-VEGF therapy increases the risk of thromboembolic events or major adverse cardiovascular events (MACEs) in patients with colorectal cancer based on real-world evidence. This retrospective cohort study was designed using linked 2009–2016 nationwide databases, including the Taiwan Cancer Registry, the National Health Insurance Research Database, and Taiwan’s National Death Index. In total, 189,708 patients newly diagnosed as having advanced colorectal cancer from 2009 to 2016 were identified and categorized into the anti-VEGF and comparator groups through age, sex, clinical stage, and diagnosis date (within 180 days) matching. Propensity score matching was further performed to balance the baseline characteristics between the two groups. The Kaplan–Meier method was used to create the cumulative incidence curves of thromboembolic events and MACEs, and log-rank tests were used to compare the differences in Kaplan–Meier curves. Competing hazard ratios (HRs) for thromboembolic events and MACEs were estimated using the Fine–Gray method when considering the competing event of death. Statistical analysis was performed using two-tailed tests with a significance level of 0.05. In total, 4635 patients were included in both the anti-VEGF group and comparator group. The risk of thromboembolic events and MACEs did not differ significantly between the two groups. After propensity score matching, the adjusted HR for MACEs or thromboembolic events was 1.040, which for MACEs was 0.989, and that for thromboembolic events was 1.028. The competing HR for MACEs or thromboembolic events was 0.921, which for MACEs, was 0.862, and that for thromboembolic events was 0.908. In conclusion, patients with advanced colorectal cancer who received anti-VEGF therapy did not exhibit significantly higher risks of thromboembolic events and MACEs than those without anti-VEGF therapy. Our study provides real-world evidence regarding the safety of anti-VEGF therapy in Asian patients with advanced colorectal cancer.