Association Between Aortic Dissection and Systemic Exposure of Vascular Endothelial Growth Factor Pathway Inhibitors in the Japanese Adverse Drug Event Report Database.

Abstract

Angiogenesis inhibition therapy using vascular endothelial growth factor pathway inhibitors (VPIs), such as bevacizumab, sunitinib, and sorafenib, is used to treat various solid tumors. Patients treated with VPIs frequently develop hypertension. Aortic dissection involves splitting of the layers of the aortic wall, and systemic hypertension is a major predisposing risk factor. Aortic dissection is often fatal unless it is diagnosed early and aggressive treatment is initiated in a timely manner. Although VPIs have been suspected in the onset of aortic dissection in anecdotal case reports, no comparative study has assessed the link. Using disproportionality analysis1 of a large Japanese postmarketing database, we detected a signal of a potential association between aortic dissection and VPIs. To examine this signal further, we performed a comparative study within the database. The Japanese Adverse Drug Event Report (JADER) database was obtained from the webpage of the Pharmaceuticals and Medical Devices Agency (PMDA) (https://www.pmda.go.jp/). Institutional review board approval was not required because JADER is an unlinkable anonymized database open to the public. We extracted …