Low dose aspirin therapy has been shown to reduce the risk of vascular events in a wide range of primary and secondary care settings, mainly in middle-aged people. There was some evidence of its potential to reduce the rate of certain malignancies and the rate of cognitive decline in older individuals. However, part of the benefit of aspirin could be offset by a variety of adverse effects, particularly those related to increased bleeding risk.

The ASPREE Clinical Trial screened and randomized 19,114 volunteers (2,411 in the US and 16,703 in Australia) between the commencement of recruitment in March 2010 and the closure of recruitment in December 2014 (2). All participants were 70+ years of age, except US Minorities who were 65+ years. 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). Key exclusion criteria included a history of a diagnosed cardiovascular disease (CVD) event, current use of aspirin for secondary prevention, serious intercurrent illness likely to cause death within the next five years, dementia or Modified Mini-Mental State (3MS) examination score of <78/100, independence-limiting physical disability, anemia or a condition with a high bleeding risk. The full list of exclusion criteria is provided in references 1, 2.

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 study drug 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), health behaviors, lifestyle questions including basic activities of daily living, quality of life, wellbeing and recent medical history updates, hospital visitations and collection of concomitant medications. Mood was evaluated annually with the Center for Epidemiologic Studies—Depression 10 question assessment (CES-D 10) tool. Laboratory measures for hemoglobin, CVD risk (lipids and triglyceride), renal function and fasting blood glucose were collected annually. During the ASPREE Clinical Trial, physical function assessments were carried out during even years of follow-up and cognitive screening alternately during odd years. Physical function measures included a 3m gait speed assessment, at usual walking pace, and grip strength (2). Cognitive measures included the 3MS, Controlled Oral Word Association Test (COWAT), Symbol-Digit Modalities Test (SDMT), Hopkins Verbal Learning Test—Revised (HVLT-R). An exception to this alternate year timing 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 in June 2017, due to futility).

During ASPREE-XT, the annual data collected during the ASPREE Clinical Trial continued, with annual measures of physical function and all cognitive measures (with Color Trails added) 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, with plasma HbA1c replacing fasting blood glucose.

The ASPREE Clinical Trial assessed the effects of low dose (100mg) daily aspirin versus placebo (randomized 50:50) on the primary endpoint of disability-free survival, the corollary of which was measured as the first event of incident dementia or persistent physical disability or death from any cause or (1). Other clinically important outcomes relevant to aspirin’s efficacy and safety, including the prevention of cardiovascular disease events, cancer, cognitive decline, depression and clinically significant bleeding, were also assessed. ASPREE-XT is an observational study that extends follow-up of the ASPREE participants, primarily to study legacy effects of randomization to aspirin versus placebo. The Bridge period was a short administrative intervening phase between the end of the intervention phase and the beginning of ASPREE-XT.

• Men and women
• African American and Hispanic persons age 65 or older
• Any person from another ethnic minority group and Caucasian persons age 70 or older
• Willing and able to provide informed consent, and willing to accept the study requirements

• A history of a diagnosed cardiovascular event
• A serious intercurrent illness likely to cause death within the next 5 years, such as terminal cancer or obstructive airways disease
• A current or recurrent condition with a high risk of major bleeding, ex: cerebral aneurysm
• Anemia
• Absolute contraindication or allergy to aspirin
• Current participation in a clinical trial
• Current continuous use of aspirin or other anti-platelet drug or anticoagulant for secondary prevention. People with previous use of aspirin for primary prevention may enter the trial, provided they agree to cease existing use of aspirin and understand that they may be subsequently randomly allocated to low dose aspirin or placebo.
• A systolic blood pressure ≥180 mmHg and / or a diastolic blood pressure ≥105 mmHg
• A history of dementia
• Severe difficulty or an inability to perform any one of the 6 Katz ADLs
• Non-compliance to taking pill

The principal findings of ASPREE is that aspirin use in healthy elderly persons did not prolong disability-free survival over a period of 5 years but led to a higher rate of major hemorrhage than placebo.

ASPREE-XT is ongoing.