Low dose aspirin therapy has been shown to reduce the risk of vascular events in a wide range of primary and secondary care settings, largely in middle-aged people. There is some evidence of its potential to reduce the rate of certain malignancies and the rate of intellectual decline in older individuals. However, part of the benefit of aspirin may be offset by a variety of adverse effects and, in particular, the balance of risks and benefits of low dose aspirin has not been established in older people.
The ASPREE Clinical Trial was needed to resolve uncertainty regarding the effects of aspirin used for primary prevention amongst older persons. Operationally, ASPREE is divided into three key phases of follow-up: the ASPREE Clinical Trial (2010 to mid June 2017), the Bridge period (mid June 2017 to 31 January 2018) and the ASPREE-eXTension (ASPREE-XT) cohort study (1 February 2018 onward). The ASPREE Clinical Trial assessed the effects of low dose (100mg) daily aspirin versus placebo on death from any cause or incident dementia or persistent physical disability (1). Other clinically important outcomes relevant to aspirin’s efficacy and safety, including the prevention of cardiovascular events, cancer and cognitive decline, were also assessed. Outcome definitions are provided in the dedicated Study Endpoints section. ASPREE-XT is an observational study that extends follow-up of the ASPREE participants, primarily to study legacy effects of randomisation to aspirin versus placebo, and the Bridge period was a short administrative intervening phase between the end of the intervention phase and the beginning of ASPREE-XT.
The ASPREE Clinical Trial screened and randomised 19,114 volunteers between the commencement of recruitment in March 2010 and the closure of recruitment in December 2014 (2). The screening process included two baseline visits (Visit 1 and Visit 2). The first visit involved initial lifestyle questions, cognitive screening and physical function screening followed by laboratory investigations and a medication compliance evaluation. The second visit included further assessments and confirmation of eligibility. In Australia, confirmation of eligibility required a clinical sign off by the participant’s usual General Practitioner (GP).
Following completion of both baseline visits, participants who satisfied all study entry criteria were randomly allocated to one of the two treatment groups and commenced the ‘follow-up’ phase of the trial during which they were sent annual supplies of study medication. During the ASPREE Clinical Trial, participants were followed up for a median of 4.7 years and phone contact with participants was attempted at three monthly intervals. The intervention phase ceased in June 2017 and participants were advised to stop taking study medication and supplies ceased. Subsequently, during ASPREE-XT, phone contact was attempted at six months following each annual visit.
During each of the follow-up phases, participants were asked to attend the clinic for annual visits that included the following: collection of physical measurements (blood pressure, weight, waist circumference and height at select visits), lifestyle questions, wellbeing and recent medical history updates, hospital visitations and collection of concomitant medications. During the ASPREE Clinical Trial, physical function screening was carried out on even years and cognitive screening alternately on odd years. Laboratory measures (including hemoglobin) were collected annually in both countries. An exception to this was that all measures were collected at participants’ close-out visits at the end of the trial; these “Milestone” visits were scheduled to occur in 2017 (the trial was originally anticipated to finish in December 2017, but a decision was made to cease due to futility in June 2017). During ASPREE-XT, physical function and select cognitive measures (Modified Mini-Mental State Examination (3MS), and Center for Epidemiologic Studies—Depression 10 question assessment (CES-D 10)) were conducted annually while other cognitive measures (Controlled Oral Word Association Test (COWAT), Symbol-Digit Modalities Test (SDMT), Hopkins Verbal Learning Test—Revised (HVLT-R) and Color Trails) were collected every year from the second ASPREE-XT annual visit (XT02). Laboratory measures were extended to include Full Blood Examination (FBE) and Complete Blood Count (CBC) annually from XT02. A detailed description of the data collection schedule is provided in the dedicated Data Collection section.
During 2017, participants completed Milestone visits that included all study assessments and an additional questionnaire about study medication, aspirin and over-the-counter medication use. Following cessation of study medication in June 2017, these Milestone visits continued until 31 January 2018. This period is referred to as the ‘Bridge’ and was immediately followed with the beginning of the ASPREE-XT cohort study from 1 February 2018. ASPREE-XT is a longitudinal observational cohort study of ASPREE participants who agreed to be followed up for an additional five years.
Two analysis data sets are available for use. The ASPREE Longitudinal Data Set (Version 3) includes data collected at Visits 1 and 2, Annual Visits 1, 2, 3, 4, 5, 6 and Milestone visits during the ASPREE Clinical Trial (i.e. between March 2010 and June 2017). This data set does not include Bridge or ASPREE-XT data. The ASPREE-XT Longitudinal Data Set (XT02) includes data captured from the time of randomisation in the ASPREE Clinical Trial through to the participant’s second ASPREE-XT annual visit date (XT02), i.e., the participant’s second annual visit after 1 February 2018. This data set includes a number of endpoint events that occurred during the ASPREE Clinical Trial but were not reported until after the ASPREE Longitudinal Data Set (Version 3) was locked, and therefore were not included in the ASPREE Longitudinal Data Set (Version 3). The ASPREE-XT Longitudinal Data Set (XT02) also includes a small number of minor modifications to the endpoint event data from the ASPREE Longitudinal Data Set (Version 3), both event occurrence and date of occurrence, as a result of continued data cleaning activities.
Please see here for a list of all ASPREE-related publications.
McNeil JJ, Woods RL, Nelson MR, Reid CM, Kirpach B, Wolfe R, et al. Effect of Aspirin on Disability-free Survival in the Healthy Elderly. N Engl J Med. 2018 Sep;379(16):1499-1508. doi: 10.1056/NEJMoa1800722.
McNeil JJ, Woods RL, Nelson MR, Murray AM, Reid CM, Kirpach B, et al. Baseline Characteristics of Participants in the ASPREE (ASPirin in Reducing Events in the Elderly) Study. J Gerontol A Biol Sci Med Sci. 2017 Oct;72(11):1586–93. doi:10.1093/gerona/glw342