The ASCEND-Eye study: effect(s) of aspirin and omega-3 fatty acids on eye disease

Thesis

Background

Aspirin and omega-3 fatty acids (FAs) have potential disease-modifying roles in diabetic retinopathy (DR) and age-related macular degeneration (AMD), but randomised evidence of these effects is limited. This thesis describes the rationale, methods and results of ASCEND-Eye; a sub-study of the ASCEND double-blind, 2x2 factorial design, randomised, placebo-controlled trial, which compared the effects of 100mg aspirin daily and, separately, 1g omega-3 FAs daily for the primary prevention of serious cardiovascular events, in 15,480 UK adults with diabetes.

Methods

Events were derived from three sources: 1) six-monthly follow-up questionnaires for ASCEND or a one-off eye questionnaire sent to a subset of participants after the parent trial ended, 2) electronic NHS Diabetic Eye Screening Programme (DESP) data and 3) responses to the National Eye Institute’s Visual Function Questionnaire-25 (NEI-VFQ-25). The primary efficacy outcome was the first occurrence of referable disease in either eye during the scheduled treatment period, a composite of referable diabetic retinopathy (≥R2) or referable diabetic maculopathy (M1), based on grading criteria defined by the National Screening Committee. The primary safety outcome was the first sight-threatening eye bleed. Secondary outcomes included incident diagnoses of AMD and the NEI-VFQ-25 composite score. Logrank methods were used for intention-to-treat analyses of time until the primary efficacy, safety, and AMD outcomes, between groups in each treatment arm. Ordinal data from the NEI-VFQ-25 were analysed using proportional odds regression methods.

Results

DESP data were obtained for 48% of those randomised in ASCEND (n=7360). During their 6.5 years of follow-up, 539 [14.6%] participants assigned to active aspirin developed referable disease compared to 522 [14.2%] in the placebo group (rate ratio 1.03; 95% confidence interval: 0.91-1.16; P = 0.64). There was no statistically significant difference in the proportion of primary efficacy events by omega-3 FA allocation. Similarly, neither treatment had a statistically significant effect on incident AMD events (n=15,480) or composite scores from the NEI-VFQ-25 (n=8839); aspirin did not increase the risk of sight-threatening eye bleeds (n=15,480).

Conclusions

ASCEND-Eye overcomes some of the methodological limitations of previous studies, providing reliable, randomised evidence of the eye-related effects of two inexpensive treatments commonly taken by those with diabetes, older people, or both. Overall, the data exclude any clinically meaningful benefits of aspirin or omega-3 FAs for DR or AMD but provide some reassurance regarding the ophthalmological safety of aspirin.

Authors: Sammons, E

• DOI: 10.5287/ora-qmgajqjag
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: omega-3 fatty acids; aspirin; diabetic retinopathy; age-related macular degeneration; randomised trial