(048) Antiangiogenic Drugs and the Risk of Arterial Dissection or Aneurysm in Patients with Metastatic Colorectal Cancer

Background: Although the mechanism of action of antiangiogenic drugs is compatible with the pathophysiological hypothesis of arterial wall damage, published data are based almost exclusively on case reports and pharmacovigilance studies.

Objectives: To investigate the association between exposure to antiangiogenic drugs and the occurrence of arterial dissection/aneurysm.

Methods: A nested case-control study was conducted within the French Système National des Données de Santé. The source cohort for the case-control analysis included all adults affiliated to the general health insurance scheme, who started an antiangiogenic or anti-EGFR drug indicated for metastatic colorectal cancer between 2012 and 2017 (baseline), and who had no history of arterial dissection/aneurysm. Patients hospitalized for arterial dissection/aneurysm between 2012 and 2019 were identified as cases, and matched up to 10 controls on age, sex, and time since baseline. The main analysis considered antiangiogenic exposure overall (exposed, unexposed). Secondary analyses considered length of exposure (current, past, unexposed) and cumulative duration of exposure, with exposure periods estimated using two methods based on i) recommended administration schedule, ii) elimination half-life. The association was estimated using conditional logistic regression models adjusted for cardiovascular status.

Results: Of the 34,733 patients of the cohort, 195 cases (0.6%) were matched to 1,950 controls. The population was predominantly male (73%), with a median age of 69 years (interquartile range: 63-73) for cases and 68 years (62-73) for controls. The main analysis involved 141 (72.3%) cases and 1,381 (70.8%) controls exposed to antiangiogenic drugs and showed no association with the occurrence of arterial dissection/aneurysm after adjustment for cardiovascular status: OR [95% CI] 1.07 [0.75; 1.52]. The absence of association was found in secondary analyses, regardless of the definition of exposure and the method used to estimate exposure periods.

Conclusions: This study showed no association between exposure to antiangiogenic drugs and the occurrence of arterial dissection/aneurysm after adjustment for cardiovascular status.