Low-dose aspirin does not prevent AMD Low-dose aspirin has no effect on the risk of age-related macular degeneration (AMD) in adult women over 10 years of treatment and follow-up, according to a new research study.

There are several possible pathways through which aspirin may exert a beneficial effect in AMD. At low doses (100 mg every other day), aspirin irreversibly inhibits platelet cyclooxygenase, resulting in a rapid and marked inhibition of platelet function and an immediate decrease in risk of blood clots. This mechanism of action is believed to underlie the protective effects of low-dose aspirin in cardiovascular disease, but seems unlikely to be an important mechanism in AMD. A more likely mechanism may involve the long-term effects of platelet inhibition on initiation and progression of atherosclerosis. Platelet inhibition may limit platelet adherence or aggregation on vascular endothelium and existing plaque, and may alter the chemotactic and adhesive properties of endothelial cells, which may be an important early pathophysiologic event in atherogenesis. It remains unclear whether atherosclerosis is an important pathogenic mechanism in AMD.

Aspirin also may influence AMD development through pathways not dependent on platelet inhibition. For example, in the vascular endothelium, aspirin has been shown to initiate production of 15-epi-lipoxin A4, which functions as a local endogenous anti-inflammatory mediator. Aspirin also may exert an antioxidant effect by protecting endothelial cells from the deleterious effects of hydrogen peroxide and other oxidative agents, and perhaps by suppressing lipid peroxidation.

Methods and Results

This study involved 39,876 healthy female health professionals aged 45 years or older from the Women's Health Study (WHS), a randomized, double-masked, placebo-controlled trial testing low-dose aspirin (100 mg every other day) and vitamin E in the primary prevention of cardiovascular disease and cancer.

Participants were assigned randomly to receive either 100 mg aspirin on alternate days or placebo and were followed up for the presence of AMD for an average of 10 years. If the participant reported the onset of visually significant AMD (reduction in best-corrected visual acuity to 20/30 or worse), their medical records were reviewed to confirm the diagnosis and level of visual acuity impairment.

After 10 years of treatment and follow-up, there were 111 cases of AMD in the aspirin group and 134 cases in the placebo group (hazard ratio: 0.82).

Discussion and Conclusions

In this large randomized trial, women assigned to alternate-day treatment with low-dose aspirin and followed up for an average of 10 years had a nonsignificant 18% reduced risk of visually significant AMD compared with women assigned to placebo. The 95% CI around this estimate could not rule out a possible beneficial effect as large as 36%, or a small harmful effect of 6% or less. Aspirin treatment seemed to have little effect on the end points of advanced AMD or all AMD cases with or without vision loss.

Observational studies provide little support for a benefit of aspirin treatment in AMD. However, these studies lacked detailed information on frequency, dosage, and duration of aspirin use, and thus had limited ability to assess the potential benefits of long-term aspirin treatment on AMD.

Only one previous randomized trial has examined aspirin treatment in AMD. In the Physicians' Health Study, men assigned to alternate-day low-dose aspirin (325 mg) had a nonsignificant 22% reduced risk of visually significant AMD (HR, 0.78) during 5 years of follow-up.

The investigators conclude that low-dose aspirin has no large beneficial effect in reducing the risk of visually significant AMD. However, a modest, but potentially important, beneficial effect on visually significant AMD could not be ruled out and warrants continued examination in other populations of men and women.

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Ophthalmology. 2009 Dec;116(12):2386-92