Objectives To evaluate whether intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) in neovascular age-related macular degeneration (nAMD) patients with prior stroke or acute myocardial infarction (AMI) are associated with increased mortality. Methods From 2005 to 2013, nAMD patients in the Taiwan National Health Insurance Research Database who received IVI of anti-VEGF and had a diagnosis of stroke/AMI prior to their first injections were defined as the IVI group. The mortality of the IVI group during the study period was compared to that of the non-IVI group, which consisted of nAMD patients who had prior stroke/AMI but were never exposed to anti-VEGF. The IVI group and the non-IVI group were 1-4 matched according to propensity score (PS), which was derived from age, sex, date of stroke/AMI and comorbidities. PS-adjusted Cox regression analyses were used to estimate the hazard ratio (HR) for mortality associated with IVI of anti-VEGF. Subgroup analyses were also performed according to the interval between stroke/AMI and IVI (<= 6 months, 6 months to 1 year, 1-2 years, >2 years). Results There were 3384 individuals in the IVI group and 13,536 individuals in the non-IVI group. The IVI group had a significantly higher mortality risk (adjusted HR = 2.37; 95% confidence interval (CI), 2.14-2.62) than the non-IVI group. Subgroup analyses revealed that elevated mortality was significant when anti-VEGF was injected within 1 year after stroke/AMI. Conclusions We found an increased mortality risk associated with IVI of anti-VEGF in nAMD patients with prior stroke/AMI compared to the mortality risk of nAMD patients with prior stroke/AMD but without exposure to anti-VEGF.
