Aspirin may double age-related macular degeneration risk

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‘Modest’ association does not support change in practice

The evidence is not yet sufficiently robust to change clinical practice regarding aspirin therapy, particularly since the strength of the association with AMD was only "modest" in this study. "These findings are, at best, hypothesis generating and should await validation in prospective randomized studies before guiding clinical practice or patient behavior.

Dr. Sanjay Kaul

"Maintaining the status quo" is the most prudent approach, particularly in the setting of secondary prevention, "where the benefits of aspirin are indisputable and greatly exceed the risk," they said.

"In the final analysis, decisions about aspirin use are best made by balancing the risks against the benefits in the context of each individual’s medical history and value judgments."

Dr. Sanjay Kaul and Dr. George A. Diamond are in the division of cardiology at Cedars-Sinai Medical Center, Los Angeles. They reported no financial conflicts of interest. These remarks were taken from their invited commentary accompanying Dr. Liew’s report (JAMA Intern. Med. 2013 Jan. 21 [doi:10.1001/jamainternmed.2013.2530]).



The use of aspirin therapy approximately doubled the risk that age-related macular degeneration would develop over a period of 10-15 years in a secondary analysis of data in the Blue Mountain Eye Study, which was published online Jan. 21 in JAMA Internal Medicine.

The regular use of aspirin was significantly associated with an increased incidence of neovascular (wet) age-related macular degeneration (AMD), with an odds ratio of 2.37, independently of cardiovascular disease (CVD), smoking status, and numerous potentially confounding factors. However, "this potential risk appears to be small (3.7% after 15 years) and should be balanced with the significant morbidity and mortality of suboptimally treated CVD," said Gerald Liew, Ph.D., of the center for vision research, department of ophthalmology, University of Sydney, and his associates.

"Given the widespread use of aspirin, any increased risk of disabling conditions and morbidity will be significant and affect many people," they noted.

Several previous studies have examined the relationship between aspirin therapy and AMD, but the findings have been inconsistent. Dr. Liew and his colleagues performed a prospective study using the largest cohort and the longest follow-up to date. Their study subjects were 2,389 participants in the Blue Mountain Eye Study, a population-based cohort study of eye disease in urban Australians aged 49 years or older.

Aspirin use was determined from the subjects’ responses to a detailed questionnaire at baseline. "Although we did not collect information on aspirin dosage, most aspirin use in Australia is prescribed at 150 mg daily," the researchers said.

A total of 257 subjects (10.8%) used aspirin therapy.

At 15-year follow-up, 63 subjects had developed neovascular AMD.

Among subjects taking aspirin therapy, the cumulative rate of neovascular AMD was 1.9% at 5 years, 7% at 10 years, and 9.3% at 15 years. In comparison, these rates were 0.8% at 5 years, 1.6% at 10 years, and 3.7% at 15 years among subjects who did not take aspirin regularly.

The increase in risk became significant only after 10-15 years, "suggesting that cumulative dosage is important in pathogenesis" of neovascular AMD, the investigators said.

This long lead time also may explain why several previous studies that had shorter follow-up failed to detect the association, they added.

After the data were adjusted to account for subject age, sex, and smoking status, aspirin therapy was significantly associated with an increased incidence of neovascular AMD, with an odds ratio of 2.37. This association remained unchanged after further adjustment for history of CVD, BMI, and blood pressure.

Aspirin therapy was not associated with the risk of geographic (dry) AMD.

The rate of neovascular AMD rose with increasing use of aspirin, from 2.2% among people who never took aspirin to 2.9% among occasional users to 5.8% among regular users, Dr. Liew and his associates said (JAMA Intern. Med. 2013 Jan. 21 [doi:10.1001/jamainternmed.2013.1583]).

The correlation between aspirin therapy and neovascular AMD remained robust in a further analysis of the data that adjusted for numerous risk factors and protective factors, such as white blood cell count, dietary factors, cholesterol levels, and the presence or absence of diabetes. The odds ratio was 2.05 in this analysis.

"Because aspirin use is strongly associated with painful conditions and CVD, we examined whether other medications associated with these conditions had a similar association with neovascular AMD," the investigators wrote. Acetaminophen, beta-blockers, and other drugs showed no significant associations with AMD.

"Although aspirin is one of the most effective CVD treatments and reduces recurrent CVD events by one-fifth, some meta-analyses have called into question the efficacy of aspirin use in CVD primary prevention and highlighted the significant adverse effects, such as increased gastrointestinal, intracerebral, and extracranial hemorrhage. Our study now raises the possibility that the risk of neovascular AMD may also need to be considered," Dr. Liew and his associates wrote.

At this time "there is insufficient evidence to recommend changing clinical practice, except perhaps in patients" who have strong risk factors for AMD, they added.

This study was supported by the National Health and Medical Research Council Australia. No financial conflicts of interest were reported.

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