According to Jie Jin Wang, PhD, of the University of Sydney, and colleagues, 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).
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).
In an invited commentary, Sanjay Kaul, MD, and George A. Diamond, MD, of Cedars-Sinai Medical Center in Los Angeles, wrote, "The evidence is insufficient to adjudicate the relationship between aspirin and age-related macular degeneration, thereby challenging causal inferences."
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, they 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.
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. "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 from 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.
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.
- 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.
- In this study, regular aspirin use was associated with increased risk of incident neovascular age-related macular degeneration, independent of a history of cardiovascular disease and smoking.