Effect of Low-Dose Aspirin on the Course of Age-Related Macular Degeneration: A Secondary Analysis of the ASPREE Randomized Clinical Trial

Abstract

Importance: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in old age. There is no proven intervention to prevent AMD and, apart from lifestyle, nutritional, and supplement advice, there is no intervention to delay its progression.

Objective: To determine the impact of long-term low-dose aspirin on the incidence and progression of AMD.

Design, setting and participants: The Aspirin in Reducing Events in the Elderly-AMD (ASPREE-AMD) study was an Australian-based substudy of the ASPREE trial, a multicenter, international, randomized, double-masked, placebo-clinical trial investigating the efficacy of low-dose aspirin in prolonging disability-free survival among older individuals. Retinal photography was conducted at baseline from March 2010 to January 2015, then 3 and 5 years after randomization. AMD status was determined using color retinal images and treatment records. Australian participants in ASPREE aged 70 years and older without dementia, independence-limiting physical disability, cardiovascular disease, or chronic illness limiting 5-year survival and with gradable retinal images at baseline were included. Data were analyzed from December 2022 to December 2023.

Interventions: Aspirin (100 mg daily, enteric coated) or placebo.

Main outcomes and measures: Incidence of AMD and progression from early/intermediate to late AMD. Outcomes were analyzed by modified intention-to-treat analysis.

Results: A total of 4993 participants were enrolled in this substudy. Baseline characteristics were similar between groups. At the time of sponsor-determined trial termination, retinal follow-up data were available for 3208 participants, 3171 of whom were analyzed for AMD incidence and progression, with a median (IQR) age of 73.5 (71.5-76.4) years and even sex distribution (1619 [51%] female). Median (IQR) follow-up time was 3.1 (3.0-3.5) years. Cumulative AMD incidence was 195 of 1004 (19.4%) in the aspirin group and 187 of 979 (19.1%) in the placebo group (relative risk [RR], 1.02; 95% CI, 0.85-1.22; P = .86). Cumulative progression from early/intermediate AMD to late AMD was observed in 14 of 615 (2.3%) participants in the aspirin group and 18 of 573 (3.1%) in the placebo group (RR, 0.72; 95% CI, 0.36-1.44; P = .36).

Conclusions and relevance: In this trial, low-dose aspirin administered for 3 years did not affect the incidence of AMD. The evidence was weaker for progression of AMD due to low number of progressed cases. Overall, these results do not support suggestion that low-dose daily aspirin prevents the development or progression of AMD.

Trial registration: anzctr.org Identifier: ACTRN12613000755730.

Figure 1.. Participant Numbers in the Aspirin in Reducing Events in the Elderly–Age-Related Macular Degeneration (ASPREE-AMD) Substudy of the ASPREE Randomized Clinical Trial

^aIncluded the latest images from 3-year or 5-year follow-up, captured before trial termination. ^b5456 Person-years of follow-up. ^c5737 Person-years of follow-up. ^dIncluded the latest images from 3-year or 5-year follow-up, captured before and up to 6 months after discontinuation of the randomized treatment in June 2017; follow-up and grading of retinal images continued until mid-2022 (the study was extended due to the interruption caused by the COVID-19 pandemic), and participants remained masked to randomization code until mid-2018 when the main outcomes of the ASPREE trial were published. ^eTotal 6989 person-years of follow-up. ^fTotal 7391 person-years of follow-up.

Figure 2.. Effect of Covariates on the Association Between Aspirin vs Placebo Allocation and All Age-Related Macular Degeneration (AMD) Incidence

BMI indicates body mass index, calculated as weight in kilograms divided by height in meters squared.