Translational vision science & technology · 2026
Association Between PCSK9 Inhibitor Use and Risk of Age-Related Macular Degeneration.
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Tsai Chien-Yun, Weng Chien-Hsiang, Tsai Ching-Yao, Sheen Yi Jing, Chen Jun-Peng, Chen Hsian-Min, Wang I-Jong, Chou Chien-Chih
Аннотация
PURPOSE: Age-related macular degeneration (AMD) has been linked to systemic lipid imbalance, vascular dysfunction, and inflammation. The ocular effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a novel class of lipid-lowering agents, have not been established. We evaluated whether PCSK9 inhibitor use is associated with reduced AMD risk compared with statin therapy.
METHODS: We conducted a retrospective propensity score-matched cohort study using the TriNetX multinational electronic health record database (2015-2024) with up to 5 years of follow-up. Adults aged ≥50 years with hyperlipidemia but no prior retinal disease were included. Participants were assigned to PCSK9 inhibitor or statin therapy groups and matched 1:1 based on demographic, clinical, and laboratory variables. Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs), and Kaplan-Meier analyses illustrated cumulative AMD incidence.
RESULTS: Among 56,660 matched participants, PCSK9 inhibitor use was associated with a significantly lower risk of AMD compared with statin therapy (HR, 0.82; 95% CI, 0.73-0.90). The association remained robust in sensitivity analyses across different follow-up intervals. Stratified analyses showed consistent findings in both age groups (50-75 and ≥75 years), male participants, those without type 2 diabetes, nonobese individuals, and those with <2 years of hyperlipidemia duration.
CONCLUSIONS: In this large real-world cohort, PCSK9 inhibitor use was associated with a lower AMD risk compared with statin monotherapy. Prospective studies are needed to confirm causality.
TRANSLATIONAL RELEVANCE: This study supports further evaluation of PCSK9 inhibition as a potential strategy to modify AMD risk.
METHODS: We conducted a retrospective propensity score-matched cohort study using the TriNetX multinational electronic health record database (2015-2024) with up to 5 years of follow-up. Adults aged ≥50 years with hyperlipidemia but no prior retinal disease were included. Participants were assigned to PCSK9 inhibitor or statin therapy groups and matched 1:1 based on demographic, clinical, and laboratory variables. Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs), and Kaplan-Meier analyses illustrated cumulative AMD incidence.
RESULTS: Among 56,660 matched participants, PCSK9 inhibitor use was associated with a significantly lower risk of AMD compared with statin therapy (HR, 0.82; 95% CI, 0.73-0.90). The association remained robust in sensitivity analyses across different follow-up intervals. Stratified analyses showed consistent findings in both age groups (50-75 and ≥75 years), male participants, those without type 2 diabetes, nonobese individuals, and those with <2 years of hyperlipidemia duration.
CONCLUSIONS: In this large real-world cohort, PCSK9 inhibitor use was associated with a lower AMD risk compared with statin monotherapy. Prospective studies are needed to confirm causality.
TRANSLATIONAL RELEVANCE: This study supports further evaluation of PCSK9 inhibition as a potential strategy to modify AMD risk.