Low-dose aspirin for AMD prevention? ASPREE data show no benefit

Use of aspirin at 100 mg per day proved unsuccessful at reducing the incidence of age-related macular degeneration (AMD) in a large cohort of older healthy individuals, according to medium-term data from the AMD substudy of the Aspirin in Reducing Events in the Elderly (ASPREE) trial.

Cumulative AMD incidence at a median follow-up of 3.09 years was similar in the aspirin and placebo groups (19.4 percent vs 19.1 percent; relative risk [RR], 1.02, 95 percent confidence interval [CI], 0.85–1.22; p=0.86). [JAMA Ophthalmol 2024;doi:10.1001/jamaophthalmol.2024.1584]

The respective rates of cumulative progression from early/intermediate AMD to late AMD were 2.3 percent and 3.1 percent (RR, 0.72, 95 percent CI, 0.36–1.44; p=0.36).

“Due to early termination of the ASPREE trial, with nearly half the expected retinal follow-up data not available, the number of cases progressed to late AMD was low,” the investigators noted.

“There was no subgroup of participants in whom the effects were significantly different from the main results. In particular, the impact of aspirin on AMD incidence was not influenced by age, smoking or alcohol use, sex, BMI, hypertension, or the use of statin medications. In addition, there was no evidence to suggest that late AMD, particularly nAMD, was more likely to occur in the group randomized to low-dose aspirin,” they pointed out.

Anti-inflammatory

Given aspirin’s anti-inflammatory property and the potential role of inflammation in AMD, the drug has emerged as a candidate therapy for AMD. [Am J Ophthalmol 2002;134:411-431; Schrör  K . Inflammation, pain, and fever, second edition. In: Acetylsalicylic Acid. Wiley‐VCH: Verlag, 2016]

Prior research hinted at the benefit of aspirin for reducing AMD risk or progression. One was the Physicians’ Health Study, where 5-year treatment yielded a risk reduction of 23 percent (RR, 0.77, 95 percent CI, 0.54–1.11). Another was the longer Women’s Health Study in which 10-year treatment resulted in an 18-percent risk decrease (RR, 0.82, 95 percent CI, 0.64–1.06). [Arch Ophthalmol 2001;119:1143-1149; Ophthalmology 2009;116:2386-2392]

“Despite the large sample sizes and longer length of aspirin exposure in both of those studies, neither result was statistically significant. Both trials were limited by reliance on self-reported AMD status, confirmed by medical reports. Self-reporting is known to be inaccurate, especially for early stages of AMD,” the investigators said. [Eye 2023;38:698-706; Ophthalmology 2021;128:1736-1747; Health Technol Assess 2022;26:1-142]

Taken together, the studies do not support the suggestion that low-dose daily aspirin prevents the development or progression of AMD, they added.

The ASPREE-AMD substudy involved 4,993 participants, of which 3,171 were included in the analysis for AMD incidence and progression. Baseline characteristics were comparable between the aspirin and placebo groups. Retinal follow-up data were available for 3,208 participants (median age 73.5 years, 51 percent female) at the time of trial termination.

The analysis had several limitations, including the administration of low-dose aspirin or placebo to approximately 3 years, which according to the investigators is a relatively short time frame in the evolution of AMD, and the use of nonmydriatic color fundus images rather than mydriatic and multimodal imaging for AMD diagnosis. Finally, the study population was limited to older people in relatively good health and of European ancestry.