Aspirin Linked to Greater Macular Degeneration Risk

October 16, 2020
Kenneth Bender, PharmD, MA

A large population study in Taiwan found regular use of aspirin for prevention of cardiac events increased risk for age-related macular degeneration.

Regular use of aspirin for its cardioprotective effect was associated with an increased risk for developing age-related macular degeneration (AMD), in a large population study in Taiwan.

Ching-Lan Cheng, PhD, Health Outcome Research Center and the Department of Pharmacy, National Cheng Kung University in Taiwan, and colleagues accessed data from the National Health Insurance Research Database to establish age- and gender-matched cohorts for aspirin and non-aspirin users.

The investigators point out that they had an opportunity to compare large populations that isn’t available in many Western countries, where use of the over-the-counter product is not covered or tracked by insurance programs.

“Besides, the aspirin dose was uniform—100mg/day—due to NIH policy, so the quantitative estimate of aspirin was accurate,” Cheng and colleagues noted. “The study number is large to present real-word evidence of aspirin use. For relatively rare disease like AMD, our study provided enough power to discover the low incidence events and possible association.”

The study population comprised 204,085 individuals using aspirin and 478,048 non-users, most in the age range of 45-64 years; identified in 3 sets of data from 2002 to 2012. Criteria for excluding individuals from the analysis included a previous history of AMD diagnosis and previous use of aspirin 180 days before the index date.

The investigators sought to control for smoking, a known risk factor for AMD that was not referenced in the data base, through several statistical approaches for unmeasured confounding factors.

Cheng and colleagues calculated that the risk of aspirin users developing AMD was 11.95 per thousand person-year, compared to 3.92 per thousand person-year for non-users. They noted that their finding might not be generalizable to other populations; and specifically that a subtype of AMD, polypoidal choroidal vasculopathy (PCV), is characteristically higher in Asian populations than in Caucasians.

The investigators also note that the literature on the putative association is mixed. “Although our finding was consistent with many observational studies from real-world population, some other studies had different conclusion,” Cheng and colleagues acknowledged.

The investigators found fault with several of the studies with findings that were contrary to theirs. In several, they found inadequate controlling for the heterogeneity of the populations, and a shorter study period than they used. They pointed to one study that principally considered an association between smoking and AMD, and another that was examining other medications besides aspirin.

There are several possible mechanisms for the development of AMD, according to Cheng and colleagues. Aspirin inhibits factors which, in turn, could reduce the synthesis of prostacyclin, an important endothelium-derived vasodilator, which could contribute to hypoxia and to neovascularization.

The anticoagulant property of aspirin also has the potential to enhance the degree of choroidal neovascularization, they posited.

“In an injured environment like AMD, aspirin probably enhances the growth of aberrant vessels, thus leads to higher chance of vessels rupture and AMD progression,” the investigators suggested.

Cheng and colleagues concluded the risk of AMD in their large study population was substantially higher with regular use of aspirin, and so recommended regular visual acuity and funduscopic examinations.

The study, “ Risk of Age-Related Macular Degeneration in Aspirin Users and Non-Aspirin Users: A Population-Based Cohort Study in Taiwan,“ was published online in Pharmacoepidemiology & Drug Safety.