Systemic thromboembolic adverse events in patients treated with intravitreal anti-VEGF drugs for neovascular age-related macular degeneration: an update

Abstract

Introduction: Intravitreal anti-VEGF is the most effective therapy for wet AMD, although systemic effects on the endothelium cannot be excluded. Areas covered: The purpose of this review was to evaluate risk of thromboembolic events associated with intravitreal anti-VEGF. Expert opinion: Current data are insufficient to confirm the safety of these compounds, due to the paucity of specific studies. Thus, pharmacovigilance for all anti-VEGF should be improved to verify the true role of anti-VEGF in the occurrence of systemic adverse events.

Intravitreal Bevacizumab in Neovascular Age-Related Macular Degeneration as First Choice: a New Italian Ruling

“…Intravitreal anti-VEGF drugs pass in to the systemic circulation and are able to decrease the plasma-free VEGF [8], theoretically increasing the risk of systemic thromboembolic events [16]. Of note, anti-VEGF molecules containing the antibody fragment crystallizable (Fc) region (bevacizumab and aflibercept) can remain in circulation longer than the anti-VEGF agents without the Fc region (ranibizumab) [8], resulting a longer half-life, slower systemic catabolism and a stronger decrease of plasma-free VEGF.…”

“…On the other hand, the risk of thromboembolic events could be underestimated in real life setting compared to RCTs data. Indeed, patients with history of stroke or myocardial infarction are usually excluded from sponsored multicentre clinical trials [16]. Moreover RCTs are designed to primarily assess the efficacy of drugs rather than their safety [16].…”

“…Indeed, patients with history of stroke or myocardial infarction are usually excluded from sponsored multicentre clinical trials [16]. Moreover RCTs are designed to primarily assess the efficacy of drugs rather than their safety [16]. Thus, to date it is not possible to definitely answer the question whether there is a definite increased cardiovascular risk of using anti-VEGF agents in such patients who are eligible for treatment.…”

“…Knowledge based on scientific evidence must guide our medical decisions and not the marketing status [27]. At present, there is no definite evidence-based reason not to use intravitreal bevacizumab because of systemic safety issues [7,16] (Table 1). Intravitreal anti-VEGF drugs pass into the systemic circulation and are able to decrease the plasma-free VEGF.…”

Intravitreal anti-VEGF agents and cardiovascular risk

“…However, caution is necessary in patients with recent thromboembolic events or myocardial infarction. It could be safer to use drugs with short systemic half-life that do not accumulate in the serum, like Ranibizumab or Pegaptamib or alternate drugs with longer plasma half-lives, which have the Fc fragment, with drugs with short plasma half-lives, without Fc fragment (82).…”