0191: Cardiovascular events and bleeding risk associated with intravitreal anti-VEGF monoclonal antibodies: systematic review and meta-analysis

Abstract

Few data exists regarding the systemic safety of intravitreal anti-VEGF monoclonal antibodies (MAb) use in people with neovascular age-related macular degeneration (AMD), diabetic macular oedema (DMO) or retinal vein occlusions (RVO). We performed a systematic review and meta-analysis to evaluate the risk of major cardiovascular (MCE) and nonocular hemorrhagic (NHE) events in AMD, DMO or RVO patients receiving intravitreal anti-VEGF MAb. We included randomized controlled trials (RCT) comparing ranibizumab or bevacizumab to no treatment or non-anti-VEGF treatments, or ranibizumab to bevacizumab, in AMD, DMO or RVO patients. We used fixed effect model and reported results as odds-ratios and their 95% CI. Primary endpoints were major cardiovascular and nonocular hemorrhagic events. 21 RCT were retrieved (9557 patients). Anti-VEGF-MAb did not significantly increase the risk of MCE events (1.18 [0.81, 1.71]) or NHE (1.42 [0.95, 2.13]) when compared to control. Bevacizumab did not increase the risk of MCE (0.94 [0.59, 1.52]) or NHE (2.56 [0.78, 8.38]) when compared to ranibizumab, but significantly increased Venous Thromboembolic Events (VTE 3.45 [1.25, 9.54]). Subgroup analysis showed a significant increase of NHE in AMD patients in ranibizumab vs control (1.57 [1.01, 2.44]). Anti-VEGF-MAb did not significantly increased overall mortality (1.53 [0.92, 2.56]), cardiovascular mortality (1.29 [0.70, 2.37]), stroke (1.61 [0.85, 3.05]), MI (0.92 [0.54, 1.59]), VTE (1.39, [0.17, 11.38]), or hypertension (0.97 [0.71, 1.32]). the available clinical evidence showed that anti-VEGF-MAbs were not associated with significant increases in risks of MCE or NHE, but studies and meta-analysis were not powered enough to correctly assess these risks. Increased risks of VTE with bevacizumab and nonocular hemorrhagic events in older AMD patients with ranibizumab should also be cautiously interpreted, as more safety data are needed