Regular aspirin use was associated with an elevated risk for neovascular age-related macular degeneration, an Australian study suggested, but actual causality remains uncertain. After adjustment for age, sex, and history of smoking, the odds ratio for macular degeneration in aspirin users was 2.37 (95% CI 1.25 to 4.49), according to Jie Jin Wang, PhD, of the University of Sydney, and colleagues.
With further adjustment for body mass index, systolic blood pressure, and history of cardiovascular disease (CVD), the association remained (OR 2.46, 95% CI 1.25 to 4.83), the researchers reported online inJAMA Internal Medicine.
However, “the evidence is insufficient to adjudicate the relationship between aspirin and [age-related macular degeneration], thereby challenging causal inferences,” Sanjay Kaul, MD, and George A. Diamond, MD, of Cedars-Sinai Medical Center in Los Angeles, wrote in an invited commentary. A recent cross-sectional study suggested a possible link between neovascular age-related macular degeneration and routine aspirin use, but other studies have yielded conflicting findings.
To prospectively examine this potential link, Wang and colleagues analyzed data from the Blue Mountains Eye Study, which included 2,389 Australians ages 49 and older. Retinal examinations were done every 5 years, and lesions classified as neovascular, or wet macular degeneration, or geographic atrophy, also known as dry macular degeneration.
Aspirin use was reported on a structured questionnaire, and information on relevant risk factors was obtained during physical examination and history reports.
A total of 257 participants were regular aspirin users. Compared with nonusers, they were older and more often had conditions such as diabetes, cardiovascular disease, or elevated blood pressure.
During 15 years of follow-up, age-related wet macular degeneration was identified in 63 individuals.
Among regular users, the cumulative incidence was 1.9%, 7%, and 9.3% at years 5, 10, and 15, while the incidence among nonusers was 0. 8%, 1.6%, and 3.7%, respectively. The incidence of neovascular macular degeneration rose with more frequent aspirin use, increasing from 2.2% in those who never took aspirin, to 2.9% for those who used it only occasionally, and 5.8% for those who took aspirin routinely. Aspirin use was not associated with risk for geographic atrophy.
Additional secondary analyses found that the risk was four times higher in patients with a history of CVD (OR 4.36, 95% CI 1.24 to 15.32) and in those without a polymorphism on CFHY402H, a gene involved in the complement pathway that has been linked with macular degeneration (OR 4.17, 95% CI 1.05 to 16.49). The researchers also considered whether other medications often taken by aspirin users, such as acetaminophen and beta-blockers, might influence risk, and the results were negative. These results create a quandary for the many patients using aspirin, particularly those taking the drug as secondary prevention of CVD, according to Wang’s group. “Aspirin is one of the most effective CVD treatments and reduces recurrent CVD events by one-fifth,” they observed. However, significant adverse events can occur, such as cerebral and gastrointestinal bleeding. “Our present study now raises the possibility that the risk of neovascular [age-related macular degeneration] may also need to be considered,” they stated.
Nonetheless, they conceded that the risk is small, at slightly under 4% over 15 years, and the evidence is thus far insufficient to support a change in practice away f rom widespread aspirin use, except for patients at very high risk for macular degeneration. Any risk-benefit analysis also must consider the availability of effective — but expensive — treatments for neovascular age-related macular degeneration. “Any decision concerning whether to stop aspirin is thus complex and needs to be individualized,” they wrote. Limitations of the study included the possibility of confounding by indication and a lack of information on the reasons why participants were taking aspirin.
In their invited commentary, Kaul and Diamond wrote, “These findings are, at best, hypothesis-generating that should await validation in prospective randomized studies before guiding clinical practice or patient behavior.”
They also advised that the choice of whether to use aspirin should focus on whether the indication is for secondary CVD prevention, “where the benefits of aspirin are indisputable and greatly exceed the risk,” or for primary prevention, where the evidence is less clear, as well as the extent of the person’s risk for macular degeneration and bleeding. “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,” they added. Other experts, such as Shawn Wilker, MD, of University Hospitals Case Medical Center in Cleveland, agreed on the importance of individual risk. “I think a reasonable circumstance when you could ask a patient not to take aspirin might be one in which there is a very low risk of mortality from cardiovascular disease or if that person is at very great risk of losing vision from macular degeneration,” Wilker said in an interview. Journal editor Kenneth E. Covinsky, MD, also weighed in in an editor’s note, stating that “as with many good studies, the data are not definitive enough to suggest changes in clinical practice.” “Rather, we hope the study galvanizes more research on the relationship between aspirin and macular degeneration,” Covinsky wrote.
The study was funded by the National Health & Medical Research Council Australia.
All authors and commentators reported that they had no financial conflicts.
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