Projects per year
Project Details
Description
OVERALL RESEARCH PLAN - ABSTRACT / SUMMARY
In the U.S., low dose aspirin (LDA) is one of the most widely used medications given its established role in the
secondary prevention of cardiovascular disease (CVD). In recent years, several expert bodies, including the
U.S. Preventive Services Task Force (USPSTF), have recommended the routine use of LDA for the primary
prevention of both CVD and colorectal cancer (CRC) based on substantial data from prior randomized
controlled trials (RCTs) primarily conducted among younger adults. However, for adults aged 70+, the
USPSTF deemed current evidence supporting a net benefit insufficient. Furthermore, the need to prolong
healthy independent life, free of dementia and significant disability, is critical given the rising social and
economic costs of the increasingly aging population. To address these knowledge gaps, the NIA/NCI-
sponsored ASPirin in Reducing Events in the Elderly (ASPREE) study was developed as a ground-breaking
RCT that recruited 19,114 initially healthy older individuals aged 70+ years (65+ for U.S. minorities) from 2010-
2014 in the U.S. and Australia to examine whether initiation of 5 years of low-dose daily aspirin (LDA; 100
mg/day) prolonged the healthy lifespan of older adults. In June 2017, the randomized treatment phase of
ASPREE was suspended after a median of 4.6 years of treatment due to lack of an effect of LDA on the
primary outcome of disability-free survival (DFS). For secondary outcomes, LDA unexpectedly was associated
with an increased risk of all-cause mortality (HR 1.14; 95% CI, 1.01,1.28) driven by an excess of deaths due to
cancer, despite no increase in incident cancer. Furthermore, LDA showed a trend toward lower incident
physical disability overall. These provocative initial findings obligate continued study and follow-up of the
ASPREE cohort through this U19 proposal. Our overall goal is to generate fundamental knowledge about the
role of aspirin in older adults, a population in which aspirin's risk/benefit for primary prevention of chronic
disease has been understudied. Our overarching hypothesis is that extended follow-up of the ASPREE
cohort will demonstrate a long-term `legacy' benefit of LDA on cancer, dementia and disability. We further
hypothesize that extensive genomic, biochemical, and imaging correlates collected during follow-up will offer
unique biological insight into LDA's effects on these endpoints that may lead to mechanistically-inspired
biomarkers for more `precision' prevention approaches to chronic disease prevention. Thus, we propose to
establish ASPREE-XT to extend follow-up in ASPREE participants over the next 5 years to pursue three
Projects focused on cancer, dementia (including Alzheimer's), and physical disability that will be supported by
6 Cores, facilitating synergy and collaboration. Together, this U19, led by a multidisciplinary, international team
of leading investigators, will provide an unprecedented opportunity to define the long-term efficacy of LDA to
guide clinical recommendations and offer fundamental insights into the biological underpinnings of the leading
causes of dementia, disability and death among older adults.
Status | Active |
---|---|
Effective start/end date | 7/15/19 → 4/30/24 |
Funding
- National Institute on Aging: $8,333,959.00
- National Institute on Aging: $340,492.00
- National Institute on Aging: $238,377.00
- National Institute on Aging: $9,454,419.00
- National Institute on Aging: $7,969,915.00
- National Institute on Aging: $8,032,026.00
- National Institute on Aging: $8,509,004.00
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ConProject-006
Chan, A., Murray, A. M., McNeil, J. J. & Ryan, J. J.
5/1/23 → 4/30/24
Project: Research project
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ConProject-005
Chan, A., Murray, A. M., McNeil, J. J. & Ryan, J. J.
5/1/23 → 4/30/24
Project: Research project
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