ASPREE-AMD will attempt to determine the relationship between AMD and low-dose aspirin therapy.
Liubov Robman, MBBS, PhD
A sub-study on age-related macular degeneration (AMD), of the Aspirin in Reducing Events in the Elderly (ASPREE-AMD) study seeks to explore the effects of a 100 mg aspirin regimen on AMD incidence, development, and progression.
Study author Liubov Robman, MBBS, PhD, with the Department of Epidemiology and Preventative Medicine at Monash University in Melbourne, Australia, and the Center for Eye Research Australia at the University of Melbourne, worked with investigators to design ASPREE-AMD as a double-blind, placebo-controlled, randomized trial of the low-dose aspirin regimen in 5000 healthy Australians aged 70 and older.
The ASPREE-AMD study findings will reportedly "be of significant clinical and public interest due to a potential to identify a possible low-cost therapy for preventing AMD worldwide and to determine risk/benefit balance of aspirin usage by the AMD-affected elderly."
Because of aspirin's known anti-inflammatory properties, it is already heavily used as a means of preventing cardiovascular disease, but despite the fact that its anti-inflammatory properties could affect AMD, it is unclear to what end. Aspirin is the "world's most widely used therapeutic agent, according to Robman, so ASPREE-AMD's attempt to clarify the role aspirin plays in AMD could be crucial to understanding who might benefit more or less from a low-dose aspirin regimen.
The 5-year sub-study involves the acquisition of retinal images of both eyes, via non-mydriatic fundus photography, to diagnose and measure AMD status at baseline, 3-year, and 5-year follow up studies. Robman wrote that ASPREE-AMD will "determine whether aspirin affects the risk of retinal hemorrhage in late AMD and whether other factors such as genotype, systemic disease, inflammatory biomarkers, influence the effect of aspirin on AMD."
Because AMD is a disease that’s pathogenesis can be linked to inflammatory processes, Robman and colleagues believe that the anti-inflammatory actions associated with aspirin "may play a role in both the prevention and slowing of progression to vision loss through a low-grade inflammatory process."
Two earlier sub-studies in the United States determined that low dose aspirin regimens reported that the risk of "visually significant" AMD was reduced by more than 20% in patients receiving alternate-daily low dose aspirin regimens compared with placebo. The studies suggested that aspirin may have a positive effect on the development and progression of AMD, but Robman believes that the study populations and methods (self-reported diagnoses) "limit the weight that can be given to this evidence."
Robman noted that the results have been inconsistent, with some studies hypothesizing that aspirin may have a protective effect that can decrease the risk of AMD, and others emphasizing the potential increased risk of "sub-retinal or vitreous hemorrhages." ASPREE-AMD hopes to clarify the relationship between aspirin use and AMD in an elderly (>70) population.
All ASPREE-eligible participants were randomized to either 100 mg of enteric-coated aspirin or enteric-coated placebo, in a ratio of 1:1. The full-color retinal photography Robman and colleagues collected from ASPREE were taken with a fundus camera, and focus on the fovea and optic disk, and were screened for incident pathology and progression. Researchers can identify, via coding, images from patients who receive intravitreal anti-VEGF therapies ranibizumab and aflibercept, but not those treated with bevacizumab, as its use is "uncommon" in Australia. The identification of anti-VEGF medications is significant because those medications can, according to Robman, affect the image accuracy in retinal photography.
Robman stated that based on age-specific data, an estimated 20 % of the patient population with no AMD (n =1998) will present with early and intermediate AMD by the end of the 5-year testing. The study also estimated that among patients with early AMD (n = 1398), 35% will see their AMD progress to intermediate stages, and at least 4% of patients with early/intermediate AMD will see it progress to late AMD.
Based on these estimates, ASPREE-AMD will "provide 80% power with 1-sided alpha of 0.05 to detect: (1) 24% reduction of early/intermediate AMD incidence, (2) 20% reduction of progression from early to intermediate stage of disease and (3) 53% reduction of progression from early or intermediate stage to late stage," Robman wrote.
The study appears in Contemporary Clinical Trials Communications.