(034) Vascular Endothelial Growth Factor Pathway Inhibitors and the Risk of Aortic Aneurysm and Aortic Dissection: A Nested Case-Control Study

Background: Concerns have been raised regarding the association between the use of vascular endothelial growth factor pathway inhibitors (VPIs) and the risk of aortic aneurysm (AA) or aortic dissection (AD). However, limited evidence exists to confirm this association.

Objectives: To evaluate the association between VPIs use and the risk of AA or AD development.

Methods: This nested case-control study was conducted using the Health and Welfare Database in Taiwan. We enrolled patients with renal, hepatic, gastrointestinal, or pancreatic cancer between 2012 and 2019, with the first diagnosis date defined as the cohort entry date. Cases were identified as patients with AA/AD hospitalization after the cohort entry date and were matched in a 1 up to 5 ratio to controls based on age, sex, cancer types, cohort entry date, and the first AA/AD event date. Controls were selected from a risk set of patients who had not experienced an AA/AD event when a case occurred. The index date for cases was the date of the first AA/AD event, while controls were assigned the date of a non-AA/AD hospitalization that occurred on the same date as the index date of the matched cases. We assessed three VPIs (sorafenib, sunitinib, and pazopanib) as exposures during the risk window (cohort entry date and the index date). Non-VPIs users served as the reference group. Multivariate logistic regression models were used to calculate the association between VPIs use and AA/AD.

Results: There were 1,461 cases and 7,198 controls in this study. After multivariate logistic regression, VPI use was generally associated with an increased risk of AA/AD (OR: 2.00, 95% CI: 1.41-2.84). The higher risk was mainly from VPI-associated AD (OR: 3.09, 95% CI: 1.77-5.39), with a non-significant rise in AA risk related to VPI use. VPIs use ≤100 days before the index date was associated with a higher risk of AA/AD (OR: 2.10, 95% CI: 1.40-3.15). However, there was no significant increase in the risk of AA/AD in patients who used VPIs between 101-365 days and >365 days before the index date compared to non-VPIs users.

Conclusions: The use of VPIs is associated with an increased risk of AA and AD, with the risk predominantly arising from AD events. Healthcare providers should closely monitor patients undergoing VPIs therapy for the development of AA and AD.