Bevacizumab and ranibizumab pose a similar risk for combined systemic arteriovenous events, aflibercept poses a similar risk for arterial events compared with all other agents and ranibizumab does not increase risk of arterial events compared to sham injection. Photo: Leo Skorin, OD. Click image to enlarge.

While there is not an absolute consensus on the risk of systemic arteriovenous thrombotic effects of anti-VEGF intravitreal injection—a subject of some controversy following publication of the CATT trial over a decade ago—there is a growing body of evidence to suggest their safety. As such, researchers at the University of Toronto believed that a meta-analysis could be particularly useful, as small risk differences can then be compared. Their study, which was recently published in American Journal of Ophthalmology, found there was no significant difference in risk for combined systemic arteriovenous events between bevacizumab and ranibizumab. The same was true when comparing different anti-VEGF agents in separate subgroup analyses of arterial and venous thrombotic events.

The meta-analysis included 20 randomized clinical trials reporting on 12,833 eyes. Of these, 16 studies reported at least one treatment arm of ranibizumab, 10 (on aflibercept, nine on bevacizumab, two on faricimab and one on brolucizumab. Also, 65% of studies reported on patients with AMD, 15% studies reported on patients with DME and 20% on retinal vein occlusion (including both central and branch).

There was no significant difference in the risk of any thrombotic event between bevacizumab 1.25mg and ranibizumab 0.5mg (risk ratio; RR= 0.96). There was no significant difference between bevacizumab and ranibizumab when restricting to arterial thrombotic events (RR= 0.88) or venous thrombotic events (RR= 1.99). The risk of arterial thrombotic events was similar between aflibercept and bevacizumab (RR= 1.11), between aflibercept and ranibizumab (RR= 0.77), between brolucizumab and aflibercept (RR= 0.67) and between aflibercept and faricimab (RR = 0.96). Compared with sham treatment, neither dose of ranibizumab (either 0.5mg or 0.3mg) showed a higher risk of arterial thrombotic events.

“These findings confirm an element of systemic safety with current anti-VEGF regimens, which should be chosen based on other factors, such as agent efficacy, ocular safety, durability, preference and cost,” the authors wrote in their paper.