Comparative Risk of Arterial Thromboembolic Events Between Aflibercept and Ranibizumab in Patients with Maculopathy: A Population-Based Retrospective Cohort Study

Background: The increasing numbers of elderly patients and rising incidence of maculopathy raise concerns over arterial thromboembolic events (ATEs) with the use of intravitreal anti-vascular endothelial growth factor (VEGF) medications. Objectives: This study aimed to compare the risk of ATEs between aflibercept and ranibizumab for maculopathy. Methods: We conducted a retrospective population-based cohort study analyzing Taiwan’s National Health Insurance Database during 2011–2017 to identify patients with maculopathy receiving intravitreal aflibercept or ranibizumab. The primary outcome was any hospitalization or emergency room visit because of ATEs, including ischemic heart disease (IHD), ischemic stroke (IS), and transient ischemic attack (TIA). The secondary outcome was mortality within 30 days after occurrence of ATE. We employed propensity score methods to generate more homogeneous groups for comparison. Results: We included 5791 aflibercept users and 14,534 ranibizumab users in this study. Compared with the ranibizumab group, the aflibercept group was associated with a lower risk of ATE (hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.80–0.91), with HRs of 0.86 for IHD (95% CI 0.80–0.93), 0.87 for IS (95% CI 0.76–1.00), and 0.57 for TIA (95% CI 0.46–0.71). The risk of 30-day mortality after ATE (HR 1.39; 95% CI 0.80–2.43) and the risk of all-cause mortality (HR 1.02; 95% CI 0.89–1.17) in the aflibercept group was similar to that in the ranibizumab group. Conclusion: The use of aflibercept in patients with maculopathy was associated with a lower risk of ATE than was the use of ranibizumab. There was no difference in mortality risk between the two groups. Our study could provide strong grounds for future prospective studies to confirm the findings.