Age-Related macular degeneration, anti-vascular endothelial growth factor agents, and short-term mortality: A postmarketing medication safety and surveillance study

Purpose: To compare short-term (1 year) survival of subjects treated for exudative age-related macular degeneration (AMD) with those with AMD who received no treatment. Methods: This was a case-control study. Beneficiaries of the Veterans Health Administration aged ≥55 years with a diagnosis of AMD in fiscal years 2007-2009 were included in this study. Veterans Health Administration clinical and pharmacy data sets were linked with a national Veterans Health Administration mortality registry. Anti-vascular endothelial growth factor exposure was identified through pharmacy records, coupled to procedure code for intravitreous injection and diagnosis code of exudative AMD. Control group consisted of patients with coded diagnosis of dry AMD and no pharmacy claims for case-defining medications. Cox proportional hazard model was adjusted for age, gender, number of injections, and ocular and medical comorbidities. The main outcome measure was hazard of death according to medication exposure. Results: A total of 3,210 patients received intravitreous injections for exudative AMD. There were 117,364 nonexposed patients with dry AMD. Twelve-month all-cause mortality in the exposed and control groups were 3.9% and 4.5%, respectively. When adjusted for age, gender, and ocular and medical comorbidities, the death hazard was 0.89 (95% confidence interval, 0.74-1.06). The risk of all-cause mortality was similar for patients receiving bevacizumab and ranibizumab. Conclusion: Twelve-month all-cause mortality in a population of predominately men with exudative AMD and a high prevalence of medical comorbidities was unaffected by exposure to therapeutic levels of vitreous bevacizumab and ranibizumab. Commonly used anti-vascular endothelial growth factor agents for exudative AMD do not adversely impact short-term survival in men.