Daily Low-Dose Aspirin Fails to Prevent AMD in Older Adults

Use of daily low-dose aspirin for 3 years didn’t prevent age-related macular degeneration (AMD) in older adults, according to a secondary analysis of the randomized ASPREE trial.

Of the 3,171 patients analyzed, cumulative AMD incidence was 19.4% in the aspirin group and 19.1% in the placebo group (relative risk [RR] 1.02, 95% CI 0.85-1.22, P=0.86), reported Liubov Robman, MBBS, PhD, of Monash University in Melbourne, Australia, and colleagues in JAMA Ophthalmology.

Similarly, there was no significant difference in cumulative progression from early/intermediate AMD to late AMD between the aspirin group and the placebo group (2.3% vs 3.1%; RR 0.72, 95% CI 0.36-1.44, P=0.36).

“To our disappointment, we discovered that regular low-dose aspirin does not prevent the development of new AMD cases,” Robman told MedPage Today. “Regular low-dose aspirin use should not be recommended to prevent or treat AMD.”

Primary results from the ASPREE (Aspirin in Reducing Events in the Elderly) study showed no link between daily aspirin use and disability-free survival among healthy older adults. Analyses of ASPREE participants also showed that low-dose aspirin use did not reduce risks of fracture in this population, and increased overall gastrointestinal bleeding risk.

As the study authors explained, AMD is “the most common cause of irreversible visual impairment among older people in high-income countries.” There is no evidence-based medical intervention to prevent the disease from developing.

Bobeck Sam Modjtahedi, MD, of Kaiser Permanente in Pasadena, California, who wasn’t involved in the study, told MedPage Today that researchers have explored possible links between aspirin use and improvement in AMD for years.

“There is an immunologic and inflammatory basis for AMD development, which is why there has been interest in seeing if anti-inflammatory drugs like aspirin can modulate the disease,” he said. “Various studies have explored this question with differing results — some reporting an increased risk, no change in risk, or decreased risk in AMD, depending on how the outcomes were measured and what type of AMD was being considered.”

The study “provides unique perspectives based on its design as a randomized clinical trial, which helps limit some of the methodologic limitations of prior studies that tended to be observational and retrospective in nature,” Modjtahedi continued. “The results appear consistent with our overall impression of aspirin and AMD risk, and add to the body of literature suggesting that aspirin likely doesn’t significantly change AMD risk.”

What about larger doses of aspirin beyond the fairly small 100-mg dose used in this study? “Although other studies may find small variations based on factors like dose and duration of aspirin use,” Modjtahedi noted, “we haven’t seen a strong enough signal in the literature to suggest tweaking those variables would make a significant change in risk.”

“Even the low dose of 100 mg daily in this age group can cause major life-threatening gut and/or brain bleeding,” Robman noted. As a result, “an increase of the daily dose would not be justifiable.”

The body of evidence should guide physicians moving forward, Modjtahedi said. “Many patients and other doctors will ask ophthalmologists their opinion on aspirin. This study allows us to answer with greater confidence that aspirin use doesn’t appear to change the risk of AMD onset or progression.”

He added that research findings should also alleviate a recent concern about aspirin use — that it will boost the risk of neovascular AMD. “We can have more confidence that patients who require aspirin are not at heightened risk,” he said.

This secondary analysis looked at an Australian-based subgroup of the ASPREE trial. 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. Patients were randomized to aspirin 100 mg daily or placebo.

Participants were ages 70 and older without dementia, independence-limiting physical disability, cardiovascular disease, or chronic illness limiting 5-year survival and with gradable retinal images at baseline.

Median age was 73.5, 51% were women, and 99% were white. Less than a third had obesity (28%-30%), and 73% of both groups had hypertension. About a third (29%-31%) had prior use of statins, and 70% rated their health as excellent or very good.

When the study began, 37% of patients had early/intermediate AMD, and 1.2% had late AMD.

The lack of differences between the aspirin and placebo groups persisted after adjustment for various potential confounders.

As for limitations, the researchers noted that few patients had AMD progression, and the wide confidence interval “could not exclude a possibility of harm.”

In addition, “the administration of low-dose aspirin or placebo was limited to approximately 3 years, which is a relatively short time frame in the evolution of AMD,” they wrote, pointing out that the study population “should be primarily considered generalizable to older people in relatively good health and of European ancestry.”

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