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

Written by: Christopher Aderman, MD

July 2021

Maloney MH, Payne SR, Herrin J, Sangaralingham LR, Shah ND, Barkmeier AJ. Risk of Systemic Adverse Events after Intravitreal Bevacizumab, Ranibizumab, and Aflibercept in Routine Clinical Practice. Ophthalmology. 2021 Mar;128(3):417-424. doi: 10.1016/j.ophtha.2020.07.062. Epub 2020 Aug 8. PMID: 32781110.

An unfortunate problem we encounter not infrequently in clinic is patients who suffer cardiovascular events or strokes while being treated with intravitreal injections.  Many patients we treat for diabetic retinal disease, age-related macular degeneration, or retinal vein occlusion often have numerous co-morbid conditions and risk factors for these severe events, so we see this relatively commonly in busy practices.  This raises the question of how patients should be counseled regarding future treatment and whether a different intravitreal medication should be considered based on variability in pharmacokinetic profiles among agents and differences in serum levels of the drugs.

Dr. Maloney and colleagues addressed this important issue in a large claims study in patients treated with various anti-VEGF agents for diabetic retinal disease (DRD), age-related macular degeneration (AMD) and retinal vein occlusion (RVO).   Until this time, studies such as Protocol T have been underpowered to detect differences in rates of serious adverse events among the different anti-VEGF agents.

In this study, 87,844 patients receiving bevacizumab, ranibizumab, or aflibercept for DRD, AMD, or RVO were studied over an 11 year period from 2007-2018.  The primary outcomes were MI, CVD (including ischemic and hemorrhagic stroke, systemic embolism, and transient ischemic attack), major bleeding (including gastrointestinal, intracranial, and severe bleeding from other sites), and all-cause hospital admission.  There were no significant differences in post-injection 180-day event rates for MI, CVD, major bleeding, and all-cause hospitalization among the anti-VEGF agents.  One of the secondary analyses stratified patients on the basis of their number of injections received during the initial 45 days (1 injection vs. 2 or more injections) and identified no differences through 180 days of follow-up among the three agents.

In summary, there were no differences in serious adverse event rates among anti-VEGF agents in an 11 year study of over 87,000 patients.  This is an important study that will certainly help us in counseling our patients and will help to eliminate confusion regarding the idea of switching medications following an event.