Aspirin and age-related macular degeneration — a link missing
Published in Health News and Evidence
Date published: About this date
A recent study reports an apparent association between long term aspirin use and the development of age-related macular degeneration (AMD). This was a prospective population-based cohort study involving 2389 people, of whom 257 were identified as regular aspirin users. Participants were followed over 15 years, during which time 63 individuals out of the 2389 in the cohort had developed incident wet AMD. Results showed a small increase in risk for AMD in the regular aspirin users relative to non-regular users. However, due to various study characteristics conclusive findings cannot be drawn from this association. The evidence is not considered strong enough to recommend a change in current clinical practice in relation to aspirin use for the secondary prevention of cardiovascular disease.
- Some people may be concerned about long-term use of aspirin after reports in the consumer press about an association with AMD.
- Reassure patients with cardiovascular disease that aspirin continues to be an important preventive medicine with likely benefits exceeding the possible small increased risk of AMD.
A recent study reported an apparent association between long-term aspirin use and the development of AMD.1 This prompted a large number of media reports warning of the potential for blindness in people taking aspirin for long periods. Given the large number of people using aspirin for secondary prevention of cardiovascular disease, which is supported by current guidelines2, these reports caused considerable concern among health professionals and consumers. Closer examination of the evidence suggests the concern may largely be unfounded.
A prospective population-based cohort study recorded the incidence of AMD in 2389 people over a 15-year period. At each observation point (5, 10 and 15 years) participants were assessed for AMD and their aspirin use determined. Overall, 2132 were classified as non-regular aspirin users (aspirin used less than once per week during the previous year) and 257 as regular users (aspirin used once or more per week in the past year).1
The association between regular use of aspirin and neovascular (wet) AMD and geographic atrophy (dry AMD) was calculated. At the 15-year observation point, 63 individuals out of the 2389 people had developed incident wet AMD. The cumulative incidence of wet AMD for regular aspirin users (n = 257) was 1.9% at 5 years, 7% at 10 years and 9.3% at 15 years. After adjustment for age, sex, smoking, history of cardiovascular disease, systolic blood pressure, and body mass index, people who were regular aspirin users had a higher risk of developing wet AMD (odds ratio 2.46, 95% confidence interval 1.25 to 4.83). The authors concluded that ‘Regular aspirin use is associated with increased risk of incident neovascular AMD, independent of a history of cardiovascular disease and smoking.’1
There are a number of serious limitations to the study design:
- length of exposure to aspirin (determined by patient recollection of usage in the past year supplemented by a 30-day medicines list) was subject to recall error, and reported usage over the previous year does not guarantee that participants took aspirin on this basis for all preceding years
- dose of aspirin was not collected, but investigators relied on the assumption that ‘most aspirin use in Australia is prescribed at 150 mg daily’.1 Many people taking long-term aspirin do so without prescription, and some brands have a higher dose presentation (e.g. 300 mg tablets)
- information on reason for taking aspirin was not obtained. Because comorbidities (e.g. arthritis) would be more likely in regular aspirin users, increased use of other drugs for these conditions was considered but not adequately controlled for. Although no association was found between paracetamol or beta blockers and AMD, no other drugs were considered
- the cohort size was small with a low number of AMD cases confirmed and only 56% of the cohort eligible for follow-up were assessed at 15 years
- the study was not randomised and the cohorts were not balanced with respect to age, incidence of stroke, heart disease and diabetes, with significantly higher incidence of these conditions in the regular aspirin user group.
Despite the limitations of this study, the results and interpretations need to be evaluated in the context of the inconsistency of findings in other studies:
- the Physicians’ Health Study and the Women’s Health Study reported no increased AMD risk during 7–10 years among aspirin users3,4
- the case-controlled Age-Related Eye Disease Study (AREDS) reported that the use of anti-inflammatory medications, including aspirin, had a protective effect on dry AMD5
- data from the Beaver Dam Eye Study,6 the Blue Mountains Eye Study7 and the Rotterdam Study8 reported no association of aspirin use at baseline with the 5-year incidence of any AMD.
Much of the media commentary following publication of these findings, as well as the invited expert commentary published with the study,9 focussed on the approximate 2.5 times increased risk of developing wet AMD associated with taking aspirin. However, importantly, the absolute risk was 9.3% over the 15 years (compared with 3.7% in those not taking aspirin).
There is a multitude of shortcomings in the scope and design of this study that preclude definitive conclusions that would affect current guidelines for appropriate long-term use of aspirin. In the absence of randomised controlled trial evidence to demonstrate a link between aspirin use and AMD, the benefits of aspirin in secondary prevention of cardiovascular disease10,11 appear to far outweigh the small, if any, risk of AMD that might be suggested from this study. For people taking aspirin long term for other reasons, health professionals should be aware of these findings when balancing the risks and benefits of treatment.
- Liew G, Mitchell P, Wong TY, et al. The association of aspirin use with age-related macular degeneration. JAMA Intern Med 2013;173:258–64. [Pubmed]
- National Heart Foundation of Australia. Guidelines for the prevention detection and management of chronic heart failure in Australia. 2011. http://www.heartfoundation.org.au/SiteCollectionDocuments/Chronic_Heart_Failure_Guidelines_2011.pdf (accessed 10 October 2012).
- Christen WG, Glynn RJ, Ajani UA, et al. Age-related maculopathy in a randomized trial of low-dose aspirin among US physicians. Arch Ophthalmol 2001;119:1143–9. [Pubmed]
- Christen WG, Glynn RJ, Chew EY, et al. Low-dose aspirin and medical record-confirmed age-related macular degeneration in a randomized trial of women. Ophthalmology 2009;116:2386–92. [Pubmed]
- Clemons TE, Milton RC, Klein R, et al. Risk factors for the incidence of Advanced Age-Related Macular Degeneration in the Age-Related Eye Disease Study (AREDS) AREDS report no. 19. Ophthalmology 2005;112:533–9. [Pubmed]
- Klein R, Klein BE, Jensen SC, et al. Medication use and the 5-year incidence of early age-related maculopathy: the Beaver Dam Eye Study. Archives of Ophthalmology 2001;119:1354–9. [Pubmed]
- Wang JJ, Mitchell P, Smith W, et al. Systemic use of anti-inflammatory medications and age-related maculopathy: the Blue Mountains Eye Study. Ophthalmic Epidemiology 2003;10:37–48. [Pubmed]
- van Leeuwen R, Tomany SC, Wang JJ, et al. Is medication use associated with the incidence of early age-related maculopathy? Pooled findings from 3 continents. Ophthalmology 2004;111:1169–75. [Pubmed]
- Kaul S, Diamond GA. Relationship of aspirin use with age-related macular degeneration: association or causation?: comment on "the association of aspirin use with age-related macular degeneration". JAMA Intern Med 2013;173:264–6. [Pubmed]
- Baigent C, Blackwell L, Collins R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009;373:1849–60. [Pubmed](accessed 1August 2012).
- National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand. Reducing risk in heart disease: an expert guide to clinical practice for secondary prevention of coronary heart disease. Melbourne: National Heart Foundation of Australia, 2012. http://www.heartfoundation.org.au/SiteCollectionDocuments/Reducing-risk-in-heart-disease.pdf (accessed 1 August 2012).