Study design of ASPirin in Reducing Events in the Elderly (ASPREE): A randomized, controlled trial☆
Introduction
There is evidence that aspirin may be effective in primary prevention against a broad spectrum of diseases prevalent in the aged such as myocardial infarction, stroke, cancer and possibly dementia, yet there has been no study focused on older persons [1], [2], [3]. Aspirin also has well documented potential for harm, mainly due to bleeding into the brain, gastrointestinal tract and elsewhere, which are also more prevalent in the elderly [4]. In some diseases, such as stroke, there is the potential for both harm and benefit [1], [5]. The population 65 years of age and older have rarely been the focus of most clinical trials and have been conspicuously absent in primary prevention studies of aspirin constituting only 12% of the primary prevention study population [6], [7], [8], [9], [10], [11].
In contrast to other aspirin trials that have focused primarily on cardiovascular endpoints, ASPREE is examining whether the potential benefits of 100 mg daily aspirin for longevity and diseases associated with aging outweigh the risks associated with its use. ASPREE utilizes a unique composite primary endpoint with a trial design that examines the overall risk and benefit of aspirin in the elderly in promoting healthy independent lifespan. The secondary endpoints were selected based on the literature, raising hypotheses indicating potential benefits and/or harm associated with aspirin use.
The study was originally planned as a primary prevention cardiovascular disease (CVD) outcome study in the early 1990s to address the lack of aged participants in contemporary trials [6], [7], [12], [13]. The current iteration commenced in 2002 with the rationale still evident but expansion of the endpoints to include other prevalent diseases in the aged [8], [9], [10], [11], [14], [15]. The combination of aspirin's off-patent status and low cost limited industry participation to providing trial drug and matching placebo. Funding was obtained from the Australian National Health and Medical Research Council (NHMRC) and the National Institute on Aging (NIA). Randomization commenced in March 2010.
Section snippets
Design overview
ASPREE is a double-blind, randomized, placebo-controlled primary prevention trial with an average follow-up of 5 years, designed to assess whether daily active treatment of oral 100 mg enteric-coated aspirin will extend the duration of disability- and dementia-free life in healthy participants 65 years and older for the US minority groups of African Americans and Hispanics, with Caucasians and other minority groups 70 years and older. Participant visits occur at baseline (2 visits 1 month apart) and
Discussion
A large-scale clinical trial of aspirin in the aged is needed to capture risk and benefit in an aging population in whom life expectancy is truncated and multiple morbidity, polypharmacy, and disability are common. For example aspirin has well recognized protection against thromboembolic stroke but adverse risk for hemorrhagic stroke [1], [5]. It became obvious during the study development process that our primary endpoint needed to address these concerns and funder's requirements. The latter
Conclusion
Healthy aging is a global public health goal with the proportion of the population reaching the age of 65 years and older dramatically increasing in most developed and developing countries. Cost-effective strategies to maintain healthy active life in these populations are required to address the global burden of age-related diseases. Daily low dose aspirin has the potential to be such a strategy as a simple, readily available, cost-effective intervention to extend healthy lifespan around the
References (43)
- et al.
Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials
Lancet
(2011) - et al.
Effects of intensive blood-pressure lowering and low dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial
Lancet
(1998) The reliability of cluster and switch scores for the Controlled Oral Word Association Test
Arch Clin Neuropsychol
(2003)- et al.
Multiplicity in randomized trials I: endpoints and treatments
Lancet
(2005) Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients
Br Med J
(2002)- et al.
Anti-inflammatory drugs protect against Alzheimer disease at low doses
Arch Neurol
(2000) - et al.
Association of aspirin use with major bleeding in patients with and without diabetes
JAMA
(2012) - et al.
Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials
JAMA
(1998) Final report on the aspirin component of the ongoing Physicians' Health Study
N Engl J Med
(1989)- et al.
Randomised trial of prophylactic daily aspirin in British male doctors
BMJ
(1988)
Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice
Lancet
Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk
Lancet
A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women
N Engl J Med
Rationale for a primary prevention study using low-dose aspirin to prevent coronary and cerebrovascular disease in the elderly
JAGS
The PACE pilot study: 12-month results and implications for future primary prevention trials in the elderly. (Prevention with low-dose aspirin of cardiovascular disease in the elderly)
J Am Geriatr Soc
Rationale for a primary prevention trial in the elderly of low dose aspirin for the prevention of major adverse cardiovascular events and vascular dementia in Australian general practice. ASPirin in Reducing Events in the Elderly (ASPREE)
J Drugs Aging
Feasibility of conducting a primary prevention trial of low-dose aspirin for major adverse cardiovascular events in older people in Australia: results from the ASPirin in Reducing Events in the Elderly (ASPREE) pilot study
Med J Aust
With special feature on socioeconomic status and health
The Modified Mini-Mental State (3MS) examination
J Clin Psychol
A measure of primary sociobiological functions
Int J Health Serv
Diagnostic and statistical manual of mental disorders
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ASPREE is registered on the International Standard Randomized Controlled Trial Number Register (ISRCTN83772183). ASPREE has received project grants from the National Institute on Aging, the National Health and Medical Research Council (Australia), Heart Foundation (Australia), the National Cancer Institute and the Victorian Cancer Agency (Australia). Bayer Pharma AG provides blinded aspirin and placebo. ASPREE has multiple IRB approvals in the US and Australia.
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See Appendix A.