Risk of Systemic Adverse Events after Intravitreal Bevacizumab, Ranibizumab, and Aflibercept in Routine Clinical Practice

Written by: Joshua D. Levinson, MD

November 2020

Maloney MH, Payne SR, Herrin J, et al. Risk of Systemic Adverse Events after Intravitreal Bevacizumab, Ranibizumab, and Aflibercept in Routine Clinical Practice. Ophthalmol. Published online August 2020. doi:10.1016/j.ophtha.2020.07.062

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents have become the standard of care in the treatment of multiple retinal vascular diseases. Randomized controlled trials investigating the use of intravitreal bevacizumab, ranibizumab, and aflibercept have reported overall low rates of systemic adverse events (SAEs). However, clinical trials are typically under-powered for the analysis of uncommon, but potentially life-threatening events, such as myocardial infarction (MI) or cerebral vascular disease (CVD). Furthermore, there are limited existing data to compare the systemic risk between anti-VEGF agents in routine clinical practice. Due to differences in drug pharmacodynamics and systemic VEGF suppression, some providers may alter their choice of anti-VEGF agent in patients at perceived higher risk of systemic complications.

This study was conducted using de-identified claims from commercially-insured and Medicare-Advantage patients who received anti-VEGF injections between 2007 and 2018. Treatment indications included neovascular AMD, diabetic retinopathy and retinal vein occlusion. Primary SAE outcomes were MI, CVD, major bleeding, and all-cause hospital admission.

A total of 87,844 patients were included (69,007 bevacizumab; 10,895 ranibizumab; 7,942 aflibercept). Demographics of the groups receiving each type of anti-VEGF agent were similar. Prior to treatments, 4.0-4.6% had prior MI and 12.7-13.8% had a history of CVD.

In the first 180 days, patients received a mean of 3.2 injections, with similar averages between treatment cohorts. Mean times-to-systemic-events were 79.9 days after bevacizumab, 81.5 days after ranibizumab, and 79.1 days after aflibercept. Post-injection event rates for SAEs were similar between bevacizumab, ranibizumab and aflibercept. Secondary analysis that stratified patients based on the number of injections (1 vs 2+) during the initial 45-day period also revealed no difference in risk of SAEs between the three anti-VEGF agents.

In conclusion, this large retrospective study of 87,844 patients found no difference in the risk of MI, CVD, major bleeding or hospital admission after initiation of treatment with intravitreal bevacizumab, ranibizumab, or aflibercept. All three agents were well tolerated with low risk of serious systemic adverse events.