PCSK9 Inhibitor Use and the Risk of Age-Related Macular Degeneration in Patients with Atherosclerotic Cardiovascular...

Background/Objectives: Emerging evidence suggests that alterations in lipid metabolism may play a contributing role in the pathogenesis of age-related macular degeneration (AMD). Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a novel class of lipid-lowering agents, offer anti-inflammatory and antioxidant benefits, which may provide protective effects against AMD. We aimed to evaluate the risk of developing AMD among patients with atherosclerotic cardiovascular disease (ASCVD) who were newly treated with PCSK9 inhibitors compared with those receiving statins. Methods: This retrospective cohort study utilized data from the Global Collaborative Network within the TriNetX Research Network. Patients with ASCVD who were newly initiated on PCSK9 inhibitors or statins were identified and matched for age, sex, race, laboratory data, comorbidities, and concomitant medications. The primary outcomes were the hazard ratios (HRs) for developing AMD, dry AMD, and wet AMD. Propensity score matching (PSM) was used to adjust for baseline demographics and comorbidities. Results: After PSM, 50,102 patients were included in each group (PCSK9 inhibitor users vs. statin users). Compared to statin users, PCSK9 inhibitor users had significantly lower risks of AMD (HR, 0.81; 95% confidence interval [CI], 0.72-0.92) and dry AMD (HR, 0.78; 95% CI, 0.65-0.94), but not wet AMD (HR, 0.90; 95% CI, 0.70-1.16). Stratified and subgroup analyses showed reduced AMD risk among patients aged ≥65 years, White patients, female patients, and evolocumab users. Conclusions: In patients with ASCVD, compared with use of statins, use of PCSK9 inhibitors is associated with reduced risks of AMD and dry AMD, suggesting a potential novel strategy for managing a condition with limited therapeutic options.