Intravitreal vascular endothelial growth factor inhibitors and cardiovascular adverse drug reactions: Added value of the data of the French pharmacovigilance spontaneous reporting assessment

Abstract

Aim: To describe cardiovascular adverse reactions reported after intravitreal injections of vascular endothelial growth factor inhibitors (I-VEGF) as registered in the French Pharmacovigilance Database (FPVDB).

Methods: This retrospective study assessed spontaneous adverse drug reactions reported to the French pharmacovigilance system and registered in the FPVDB from April 2007 to June 2023. Eligible cases of thromboembolic events and arterial hypertension associated with three I-VEGFs (aflibercept, ranibizumab and bevacizumab) were selected.

Results: A total of 127 cases were included (83 for ranibizumab, 37 for aflibercept, and 7 for bevacizumab), including 21 cases of arterial hypertension and 106 cases of thromboembolic events. The median onset time for thromboembolic events ranged from 1 to 119days following injection, and from 0 to 30days for arterial hypertension. The median number of injections ranged from 1 to 24 before the occurrence of an adverse drug reaction. In 23% of cases, no risk factor was found for the occurrence of a cardiovascular or thromboembolic adverse event. In two cases, a positive rechallenge was documented.

Conclusion: The rational use of pharmacological data, some relevant spontaneous reports and some pharmacoepidemiological studies are a prompt to health professionals to take precautions in patients with risk factors requiring I-VEGF. However, European Summaries of Product Characteristics do not give a clear picture to healthcare professionals concerning the precautions to take for patients with risk factors.

Keywords: Adverse drug reaction; Aflibercept; Bevacizumab; Intravitreal injection; Pharmacovigilance; Ranibizumab; Vascular endothelial growth factor.