Cardiovascular and Mortality Risk with Intravitreal Vascular Endothelial Growth Factor Inhibitors in Patients with Diabetic Retinopathy

Objective: To investigate the cardiovascular (CV) safety associated with intravitreal anti-VEGF injections (IAVIs) in patients with diabetic retinopathy (DR). Design: Population-based cohort study using Medicare and 2 commercial insurance claims databases in the United States from January 2009 to December 2017. Subjects: Patients with DR aged >= 18 years in whom treatment with either IVAIs or laser procedure or intravitreal steroid injections was initiated. Methods: We estimated the propensity score (PS) using multivariable logistic regression models, including 85 baseline covariates and PS-matched patients in a 1:1 ratio. We estimated the pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses based on prior history of CV events were also conducted. Main Outcome Measures: A composite CV outcome of myocardial infarction (MI) or stroke, its individual components, and all-cause mortality in 180 and 365 days after treatment initiation. Results: We identified 61 508 PS-matched patients in a 1:1 ratio in whom either IVAIs or laser or steroid treatment was initiated. Compared with laser or steroid treatment, IAVIs were not associated with an increased risk of the composite CV outcome (HR, 0.95; 95% CI, 0.83-1.09), MI (HR, 0.93; 95% CI, 0.76-1.13), or stroke (HR, 0.98; 95% CI, 0.80-1.19) or the risk of all-cause mortality (HR, 1.25; 95% CI, 0.97-1.62) at 180 days of follow-up. At 365 days, the risk of the composite CV outcome, stroke, and MI remained similar between the 2 groups, although the risk of all-cause mortality was increased with IAVIs (HR, 1.35; 95% CI, 1.14-1.60). The subgroup analysis showed that the risk of all-cause mortality was increased in patients with a prior history of CV events. Conclusions: Among> 60 000patientswithDR, thosewho received IAVIs had a risk ofCVevents similar to those who received laser or steroid treatment. However, the risk of all-cause mortality was higher in patients who received IAVIs for DR. Ophthalmology Retina 2022;6:1145-1153 (c) 2022 by the American Academy of Ophthalmology