ABSTRACT
INTRODUCTION: The risk of thromboembolic events or death in patients treated with intravitreal anti-vascular endothelial growth factor (IVT anti-VEGF) is poorly described on a large scale and by molecule. This study aimed to assess the risk of myocardial infarction (MI), stroke, or death in new users of IVT aflibercept versus ranibizumab in real-world practice. METHODS: A nationwide cohort study using the French National Health Insurance databases covering 99% of the French population was conducted in patients aged 18 years or older who initiated IVT therapy with ranibizumab or aflibercept between 2014 and 2018. Patients were followed for up to 6 years until December 31, 2019. The risks of MI, stroke, and death were compared in new aflibercept versus ranibizumab users using Kaplan-Meier and multivariate Cox proportional hazards models adjusted on sociodemographic characteristics and cardiovascular disease or risk factors. Subgroup analyses were performed according to history of ischemic heart disease or stroke, diabetes, indication for treatment, sex, age, and number of IVT anti-VEGF injections. RESULTS: When compared to new users of ranibizumab (n = 174,794, mean age 76.0 ± 11.9 years, 59.2% female), new users of aflibercept (n = 76,242, mean age 76.6 ± 11.2 years, 59.2% female) did not have an increased risk of MI (n = 1523 incident MI, adjusted hazard ratio [aHR] 1.00; 95% CI 0.89-1.11), stroke (n = 2306 incident strokes, aHR 1.03; 95% CI 0.95-1.13), or death (n = 4135 deaths, aHR 0.98; 95% CI 0.92-1.05). However, a small but non-statistically significant increase in the risk of stroke was observed in new users of aflibercept versus ranibizumab among patients with diabetes (aHR 1.15; 95% CI 0.98-1.35), particularly those with diabetic macular edema (aHR 1.20; 95% CI 1.00-1.44). The remaining subgroup analyses did not change the results. CONCLUSION: Aflibercept and ranibizumab appear to have similar safety profiles with respect to the risk of MI, stroke, or death under real-world conditions of use.
ABSTRACT
PURPOSE: To describe the sociodemographic, medical and management characteristics of patients using intravitreal (IVT) anti-vascular endothelial growth factors (VEGF) in France. METHODS: An observational study was conducted in patients treated with IVT ranibizumab or aflibercept, aged 18 years or older using the French National Health Insurance Databases covering 99% of the French population. Patients currently treated in 2018 were included in a cross-sectional approach to describe treatment history over the previous 6 years. Patients newly treated between 2014 and 2018 were included in a longitudinal approach to describe treatment management during up to 6 years of follow-up. Sociodemographic characteristics and medical history were described in both populations. The analyses were performed at the patient level, as no distinction between the eyes could be made. RESULTS: A total of 224 775 current users of IVT anti-VEGF in 2018 (mean age 78.1 ± 11.3 years, 60% female) and 330 969 new users between 2014 and 2018 (mean age 75.9 ± 12.0 years, 59% female) were included. In both populations cardiovascular comorbidities or risk factors were frequent and the main treatment indications were age-related macular degeneration and diabetic macular oedema. Among current users of IVT anti-VEGF in 2018, the mean number of years receiving a treatment was 2.9 ± 2.0 years, with a mean of 13.7 ± 11.8 dispensations. In the longitudinal approach, a 26% increase in IVT anti-VEGF initiation was observed between 2014 and 2018. For new users, the mean number of years receiving a treatment was 1.6 ± 1.6 and 67% had at least three dispensations within the first three months. A treatment interruption was observed for 83% of new users and occurred on average of 6.1 ± 8.1 months after initiation. The mean number of dispensations was 4.8 ± 2.8 in the first year and 2.2 ± 2.9 in the second year. The mean number of eye monitoring examinations was 6.5 ± 4.7 in the first year and 4.6 ± 4.4 in the second year. CONCLUSION: This study described the real-world conditions of IVT anti-VEGF dispensing at the entire French population scale. Less frequent dispensations and surveillance examinations were observed than in monthly schemes applied in registration trials for IVT anti-VEGF. These results may indicate a lack of systematic monitoring associated with fewer injections and/or clinicians' preference for more flexible and personalized injection schemes than those originally recommended.
