Intravitreal anti-vascular endothelial growth factor (VEGF) drugs were not associated with an increase in major adverse cardiovascular events (MACEs) in a new systematic review and meta-analysis. The results update an earlier study by Dr. Theodora Bejan-Angoulvant of CHRU de Tours in France and colleagues that came to similar conclusions. The findings "were expected, since the dose injected intravitreally is small and systemic passage of anti-VEGF is low," Dr. Bejan-Angoulvant told Reuters Health by email. "However, an increased risk of non-ocular hemorrhagic events was confirmed, mainly observed with ranibizumab in age-related macular degeneration (AMD) patients who are also older and at increased bleeding risk." "What was not expected was to observe an increased mortality risk in diabetic patients, a result for which the level of evidence was low," she said. "However, one may not exclude that even small systemic concentrations of anti-VEGF after intravitreal injections may lead to serious adverse events in a subset of high-risk patients." Therefore, she said, "physicians are encouraged to continue monitoring and reporting of potential serious adverse events." As reported in JAMA Ophthalmology, the team searched the literature from inception to July 2020 for randomized clinical trials of adults receiving intravitreal anti-VEGF drugs for various retinal diseases. The main outcomes were MACEs and total mortality. Seventy-four randomized clinical trials were analyzed: 32 (43%) included 14,190 patients with age-related macular degeneration (AMD); 24 (32%) involved 5,424 patients with diabetic macular edema or proliferative diabetic retinopathy; 17 (23%) included 3,757 patients with retinal-vein occlusion, and one (1%) involved 122 patients with myopic choroidal neovascularization. Anti-VEGF drugs did not increase MACEs (odds ratio, 1.16; 95% confidence interval, 0.85 to 1.58) or total mortality (OR, 1.27; 95% CI, 0.82 to 1.96) compared with control treatments. As Dr. Bejan-Angoulvant noted, there an increase in the risk of death in patients with diabetic macular edema or proliferative diabetic retinopathy (OR, 1.80); however, no increase was observed in patients with AMD or retinal-vein occlusion. In addition, anti-VEGF drugs increased the risk of non-ocular hemorrhage (OR, 1.46), mainly in patients with AMD. The authors note, "Cardiologists and ophthalmologists should be aware of these safety signals, especially in patients at high risk." Dr. Stephen Jae Kim, chief of the Retina Division and program director of the Vitreoretinal Fellowship at Vanderbilt Eye Institute in Nashville, Tennessee, said the findings fit with his clinical experience. "We have not observed any increased cardiovascular adverse events in our treatment population - i.e., more than would be anticipated in this higher risk group," he told Reuters Health by email. That said, he added, "Some of us may delay treatment with intravitreal anti-VEGF agents in a patient with a recent cardiovascular event." "The major accepted risk of intravitreal anti-VEGF drugs is ocular complications, such as uveitis and endophthalmitis," noted Dr. Kim, who was not involved in the study. "Routine monitoring of complications, meticulous antiseptic intravitreal injection technique, and timely patient access to urgent and after-hour care are needed." Further, he said, "We should always continue to observe and be mindful of any possible risk of intravitreal anti-VEGF drugs, since the use of these drugs is so widespread that even rare risks can result in relatively large numbers of affected individuals." —Marilynn Larkin Source
