Non-vitamin K antagonist oral anticoagulants versus warfarin and the risk of cataract in patients with atrial fibrillation: A real-world cohort study

Background Non–vitamin K antagonist oral anticoagulants (NOACs) are newer oral anticoagulants used in patients with atrial fibrillation (AF). In contrast to warfarin, NOACs do not interfere with vitamin K–dependent pathways. Given the potential role of vitamin K in lens homeostasis and oxidative stress regulation, differences in anticoagulant class may influence cataract development. However, this association has not been previously evaluated. Purpose To evaluate the association between NOAC versus warfarin use and the risk of incident cataract in patients with AF. Methods We conducted a real-world, active-comparator, new-user cohort study emulating a target trial using the TriNetX U.S. Collaborative Network database. Adults with AF initiating NOACs or warfarin between 2015 and 2024 were included. Propensity score matching was performed to balance baseline characteristics, including demographics, comorbidities, medications, and laboratory variables. The primary outcome was newly diagnosed cataract. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Prespecified subgroup analyses were conducted by age and sex. Results After matching, 252,520 patients were included (126,260 per group; mean age 68.4 years; 38.6% female). During follow-up, cataract occurred in 7,454 NOAC users and 9,003 warfarin users. NOAC use was associated with a significantly lower risk of cataract compared with warfarin (HR 0.89, 95% CI 0.87–0.92). Subgroup analyses demonstrated a similar trend of lower cataract risk associated with NOAC use among patients aged ≥65 years (HR 0.89, 95% CI 0.86–0.92), males (HR 0.88, 95% CI 0.85–0.92), and females (HR 0.88, 95% CI 0.83–0.92). The association was not statistically significant among younger patients aged 18–64 years (HR 0.97, 95% CI 0.87–1.07). Conclusions In this large-scale real-world cohort of patients with AF, NOAC use was associated with a significantly lower risk of cataract compared with warfarin. These findings suggest a potential difference in cataract risk between NOACs and warfarin and may have implications for anticoagulant selection, particularly in older patients.