ASCEND-Eye

Purpose Preclinical studies support a protective role for aspirin in early diabetic retinopathy (DR), but the findings from randomized trials are limited. We present randomized evidence for the efficacy and safety of aspirin on DR outcomes. Design A sub-study of the ASCEND (A Study of Cardiovascular Events iN Diabetes) double-blind, randomized, placebo-controlled trial of 100mg aspirin daily for the primary prevention of serious cardiovascular events in people with diabetes. Participants 15,480 UK adults at least 40 years of age with diabetes. Methods Linkage to electronic NHS Diabetic Eye Screening Programme records in England and Wales, and confirmation of participant-reported eye events via medical record review. Logrank methods were used for intention-to-treat analyses of time until the first primary efficacy and safety outcomes. Main Outcome Measures The primary efficacy endpoint was the first post-randomization record of referable disease, a composite of referable retinopathy (R2 or R3a/s) or referable maculopathy (M1) based on the grading criteria defined by the UK National Screening Committee. The primary safety outcome was the first sight-threatening eye bleed, defined as clinically significant bleeding in the eye that resulted in unresolved visual loss or required an urgent intervention such as laser photocoagulation, vitreoretinal surgery, intraocular injection, or both. Results Linkage data were obtained for 7360 participants (48% of those randomized in ASCEND). During their mean follow-up of 6.5 years, 539 [14.6%] had a referable disease event in the aspirin group, compared to 522 [14.2%] in the placebo group (rate ratio 1.03; 95% confidence interval (CI): 0.91-1.16; P = 0.64). There was no statistically significant between-group difference in the proportions of sight-threatening eye bleed events (57 [0.7%] and 64 [0.8%] participants, respectively; rate ratio 0.89; 95% CI: 0.62-1.27). Discussion These data exclude any clinically-meaningful benefits of aspirin for diabetic retinopathy but give reassurance regarding the ophthalmological safety of aspirin.