Highlight
– Extended follow-up of the ASPREE trial (ASPREE-XT) confirms no benefit of low-dose aspirin on healthy lifespan in older community-dwelling adults.
– Low-dose aspirin did not reduce incidence of dementia, persistent physical disability, or all-cause mortality over nearly a decade.
– Aspirin use was linked to increased risk of major hemorrhagic events over the combined study period.
– These findings inform clinical decision-making regarding aspirin use for primary prevention in older adults.
Study Background and Disease Burden
The global population is aging rapidly, and maintaining a healthy lifespan—survival free from debilitating conditions such as dementia and persistent physical disability—is a key goal for public health. Dementia and physical disability impose considerable individual, familial, and societal burdens, and they are leading causes of dependency in older adults.
Aspirin, a widely used antiplatelet agent, has long been investigated for prevention of cardiovascular events. Beyond cardiovascular protection, aspirin has been hypothesized to confer additional benefits possibly influencing age-related conditions such as dementia and disability, potentially via anti-inflammatory or antithrombotic mechanisms.
The original ASPREE (Aspirin in Reducing Events in the Elderly) randomized clinical trial evaluated whether low-dose aspirin (100 mg daily) could prolong a healthy lifespan in community-dwelling adults aged predominantly 70 years and older, free of cardiovascular disease and major disability at baseline. Initial results indicated no prolongation of survival free of dementia or persistent physical disability and even noted a small increased risk of all-cause mortality with aspirin.
Given the typically long preclinical course of neurodegenerative and other aging-related diseases, the ASPREE investigators conducted the ASPREE-XT observational extension to examine potential legacy effects and longer-term consequences of aspirin use beyond the median 4.7 years of randomized treatment.
Study Design
The ASPREE trial enrolled 19,114 community-dwelling individuals aged predominantly 70 years and older from Australia and the USA between March 10, 2010, and December 24, 2014. Eligible participants were free of cardiovascular disease, dementia, or persistent physical disability at baseline. Participants were randomized to receive low-dose aspirin (100 mg daily) or placebo with a median treatment duration of 4.7 years.
After completion of the randomized trial, 15,633 participants who consented to continued follow-up entered the ASPREE-XT observational phase, with a median follow-up of 4.3 years (IQR 4.1–4.6). This extended observation allowed assessment of both the direct and potential delayed (legacy) effects of aspirin.
The primary endpoint was a composite of incident dementia, persistent physical disability, or death from any cause. Each component was adjudicated by expert panels blinded to treatment allocation. Secondary endpoints included major hemorrhagic events. Analysis employed Cox proportional hazards models under the intention-to-treat principle.
Key Findings
Among the 15,633 participants in ASPREE-XT, 56.5% were women and 6.3% identified as non-White. Annual event rates for the primary composite endpoint were similar between aspirin and placebo groups during the ASPREE-XT observational period (34.37 vs. 33.68 events per 1000 person-years; Hazard Ratio [HR] 1.02, 95% Confidence Interval [CI] 0.94–1.11; p=0.63), indicating no significant benefit of continued aspirin exposure after trial cessation.
When considering the entire study period encompassing both the randomized ASPREE phase and the ASPREE-XT extension—nearly a decade of follow-up overall—aspirin use showed no long-term benefit on the composite outcome (HR 1.01, 95% CI 0.95–1.08; p=0.65) nor on mortality alone (HR 1.06, 95% CI 0.99–1.14; p=0.10).
Regarding safety, no increased risk of major hemorrhagic events was noted during ASPREE-XT alone. However, over the combined follow-up, aspirin was associated with a statistically significant increased hazard for incident major hemorrhagic events (HR 1.24, 95% CI 1.10–1.39).
These findings reinforce that low-dose aspirin does not prolong a healthy lifespan, defined by survival free from dementia and persistent disability, in initially healthy older adults. Moreover, aspirin carries a notable bleeding risk that must be weighed against uncertain benefits.
Expert Commentary
The ASPREE and ASPREE-XT results align with emerging evidence questioning routine low-dose aspirin use for primary prevention in older adults without established cardiovascular disease. The lack of benefit on cognitive and physical disability outcomes in this extended follow-up strongly suggests aspirin is not effective for preserving overall functional healthspan.
Importantly, the increased risk of serious bleeding events confirms the need for clinical caution. Older populations are inherently at higher hemorrhagic risk, and aspirin’s antiplatelet effect, while cardioprotective in some contexts, may predispose to harm when used prophylactically without firm indications.
Limitations include potential selection bias, as participants consenting to extended follow-up may differ systematically from those who did not, and the relatively short period of randomized treatment before observation. Yet the rigor of outcome adjudication and large sample size strengthen the findings’ validity.
Clinicians should individualize aspirin therapy decisions in older adults, considering cardiovascular risk, bleeding risk, and patient preferences, while recognizing that aspirin is unlikely to extend survival free of dementia or disability.
Conclusion
The ASPREE-XT observational follow-up confirms that low-dose aspirin does not confer a prolonged healthy lifespan in older adults initially free of cardiovascular disease and functional impairment. It neither reduces dementia, persistent physical disability, nor mortality over nearly a decade. The observed increased risk of major hemorrhagic events underscores the importance of cautious aspirin use in this population.
These results should inform guidelines and clinical practice, emphasizing that aspirin is not indicated for healthy lifespan extension in community-dwelling older adults. Future research may explore alternative strategies to maintain functional independence and delay cognitive decline in aging populations.
References
Shah RC, Ryan J, Webb KL, Wolfe R, Chan A, Chong TT, Ernst ME, Espinoza SE, Flynn O, Lee SY, McNeil J, Nelson MR, Orchard SG, Reid CM, Sheets K, Stocks NP, Weerasinghe NS, Wilson ME, Woods RL, Murray AM. Aspirin and healthy lifespan in older people: main outcome of the ASPREE-XT observational study. Lancet Healthy Longev. 2026 Aug 27:100764. doi: 10.1016/j.lanhl.2025.100764. Epub ahead of print. PMID: 41043446.
Zhou Z, Hu D. Effects of aspirin on the risk of dementia in adults: A meta-analysis. Neurology. 2023;101(15):e1765-e1773. doi:10.1212/WNL.0000000000202163.
McNeil JJ, Nelson MR, Woods RL, et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med. 2018;379(16):1509-1518. doi:10.1056/NEJMoa1805819.