FOR CLINICIANS

Frequently asked questions

Q: What does the ASPREE/ASPREE-XT study involve?

A: ASPREE-XT is conducted similarly to the ASPREE clinical trial, but participants are no longer taking study tablets (100mg aspirin or a matched placebo).

Your role in ASPREE-XT

• Oversee your patients’ routine health care, including pathology. Patients do not take study tablets in ASPREE-XT.
• Receive a summary of your patient’s clinical and performance measures (e.g. cognitive changes, BP, weight, CESD-10, etc.) detected at ASPREE-XT study visits.
• As a co-investigator to ASPREE-XT, you are acknowledged for your contribution to significant public health research.
• You will be sent updates on the progress of ASPREE-XT and ASPREE publications.

Your patient’s role in ASPREE-XT

• Most ASPREE participants expressed a desire to continue in the follow-up ASPREE-XT study.
• Your ASPREE-XT patients have given consent to access their medical records, receive phone calls every 6 months, and attend face-to-face annual study visits with our research staff.
• Your patient undertakes clinical, neurocognitive and physical function measurements, pathology, and completes questionnaires for mood, quality of life, physical ability, and provides personal health, demographic, and lifestyle details.
• Medical records provide critical data for ASPREE-XT researchers to accurately adjudicate patient health outcomes for inclusion in the analysis.

Primary Care Providers (PCPs) and research staff reinforce the importance of the ASPREE study. We acknowledge their contributions and dedication to this significant research.

Frequently asked questions

Q: What are the implications of ASPREE findings for clinical practice?

• Results from the ASPREE trial are applicable to ONLY primary prevention.
• PRIMARY PREVENTION – Primary prevention aims to prevent disease or injury before it occurs, by preventing exposures to hazards, altering unhealthy or unsafe behaviors and increasing resistance to disease or injury upon exposure.
• 90% of the participants in ASPREE were not regular aspirin users. Therefore, strictly, the ASPREE results apply most clearly to those initiating aspirin for the first time. The advice about whether to continue low-dose aspirin in a person who has been taking it regularly for some time is uncertain.
• The use of low-dose aspirin for secondary prevention (after a myocardial infarction, stroke, angina, TIA, etc.) is much better established and should continue.

Frequently asked questions

Q: Why are ASPREE and ASPREE-XT looking at cancer outcomes?

Meta-analyses published in The Lancet by other researchers such as Rothwell et al. provided evidence in support of low-dose aspirin preventing cancers of the colon, oesophagus, lung and stomach.

A: ASPREE reported a slightly higher death rate amongst the aspirin-treated group than in those taking placebo.  It was mostly explained by more rapid progress of cancers that were already advanced when they were diagnosed.

This finding was based on small numbers and could have occurred by chance. Also, in many previous aspirin trials, no similar findings were observed and there was considerable evidence suggesting that aspirin may lead to a reduction in cancer.

However, studies that have described a reduction in cancer mortality (particularly colorectal cancer mortality) have found that the effect starts to appear only 5-10 years after a period of prolonged intake of aspirin. Mostly these findings have originated from studies in younger populations.

At present the existence of a cancer-reducing effect of aspirin is controversial, especially since the findings of ASPREE were published. The continued follow-up of ASPREE participants after a median 4.7 years of intervention will determine whether the early increase in cancer mortality is followed by a later decline.

View selected cancer papers here.

Frequently asked questions

Q: What happens when your patient may have cognitive decline?

A:  At every annual study visit, our research staff track the cognitive state of study participants by administering the Modified Mini-Mental State (3MS); an internationally accepted neuro-cognitive screening tool that uses a 100-point scale. The 3MS is more sensitive to cognitive change than the MMSE, which uses a 30-point scale.

If a participant’s 3MS score declines to a predetermined level (set by population normative data) at any point during the study then:

• The participant is invited to undertake further cognitive measures with specially trained ASPREE research staff.
• ASPREE staff will notify the participant’s PCP of the 3MS decline and recommend further follow-up such as referral for specialist or assessment clinic review, brain imaging, and dementia screening pathology.

Subsequently:

• Findings from additional cognitive measures are provided to the participant’s PCP and if a specialist referral is not appropriate or possible, the PCP/specialist will be asked to provide a clinical opinion on a short questionnaire (DSM-IV proforma).
• ASPREE staff seek medical documentation relevant to dementia investigations from medical practices, specialists and assessment clinics.
• Findings from routine cognitive measures (i.e. 3MS) and the specialized cognitive review, dementia investigative reports and the PCP completed DSM-IV proforma (if available) are then collated and form the basis for specialist adjudication on whether the participant has reached a dementia ‘endpoint’ during the ASPREE-XT study period.

ASPREE does not initiate clinical assessment or treatment of cognitive decline. The literature highlights the value of early diagnosis of dementia, as there are now effective interventions that may improve patient quality of life. Recent research also shows a reversible cause may be present in some cases.

Frequently asked questions

Q: How does ASPREE collect participant medical records?

All study participants have consented for trained ASPREE staff members to review their medical records and collect documentation of clinical events from their Primary Care Provider (PCP), specialist and hospital.

Medical records provide the documentation necessary for ASPREE investigators with the relevant clinical expertise, to adjudicate whether a participant has reached a predetermined study ‘endpoint’, such as cancer or dementia. This process is critical to the project’s findings and maintenance of high-quality data.

Our research staff use key terms to search medical records for evidence of clinical health events studied in the ASPREE project. For instance, key search terms used to identify stroke events include ‘stroke,’ ‘CVA’, ‘cerebrovascular accident,’ and ‘cerebral infarct.’  

PCPs are always welcome to proactively advise ASPREE of their patient’s clinical event, however, we understand that most practices are too busy. Our trained staff securely and confidentially collect this information when they review the participant’s medical record. 

Frequently asked questions

Q: What happens when patients reach a study endpoint?

A: We ask all participants to continue in the follow-up ASPREE-XT Study, attending scheduled study visits where ever possible. Tracking the ongoing health of each participant after a study endpoint is pivotal.

All health data from ASPREE participants collected for the duration of the project greatly contribute to the study’s quality and findings.

Frequently asked questions

Q: What sub-studies were incorporated into the ASPREE project?

A: Large-scale research projects take many years and costs tens of millions of dollars. Because of the cost and the logistics, such studies are infrequently undertaken. ASPREE was a rare opportunity to undertake many ancillary studies to provide important public health information. Study participants largely found sub-studies interesting and engaging. View ASPREE sub-studies here.

ASPREE-XT Study Protocol

Summary

ASPREE-XT is a longitudinal, observational follow-up study of ASPREE participants to determine whether there are long-lasting (legacy) effects of a median 4.7 years of treatment with daily low-dose aspirin on the key outcome measures of:

1) Cancer, metastases and cancer mortality
2) The composite primary ASPREE-XT outcome of dementia, disability or death
3) Secondary ASPREE-XT outcomes of all-cause mortality, dementia, physical disability, cancer, mild cognitive impairment, depression and frailty, incidence of cardiovascular disease including fatal and non-fatal stroke, major hemorrhage.

• An additional objective is to study the impact of demographic, comorbid, environmental and genomic factors on the maintenance of cognition and other aspects of health amongst older adults.
• Study methodology is based closely on the ASPREE clinical trial.
• Involves annual data collection of clinical, neurocognitive and physical function measures, mood, quality of life, physical ability, demographic and lifestyle details, pathology (FBE, HbA1c, creatinine, ACR) and/or clinical events via medical records.
• ASPREE-XT is funded by the National Institute on Aging and the National Cancer Institute (NIA and NCI; part of the National Institutes of Health, USA) and the National Health and Medical Research Council of Australia.

Download the ASPREE-XT Study Protocol

ASPREE Clinical Trial Protocol

Summary

• ASPREE (ASPirin in Reducing Events in the Elderly) was a double-blind, randomised, placebo-controlled primary prevention trial to determine whether daily active treatment of 100 mg enteric-coated aspirin extended the duration of disability-free life in healthy older adults.
• It was comprised of 19,114 community dwelling participants: 2,411 participants from centers across the United States and 16,703 participants from across south eastern Australia.
• While Australian participants were mainly Caucasians aged 70 and above, approximately half of the United States participants were ethnic minorities aged 65 years and older.
• All participants were free of overt cardiovascular disease, dementia and were otherwise healthy and able to perform basic activities of daily living (ADLs) independently at enrollment into ASPREE.
• The primary objective was to determine whether 100 mg aspirin prolonged life free of dementia, or life free of significant, persistent physical disability in the healthy elderly.
• Secondary objectives related to the effects of low-dose aspirin on the key outcome areas of death, cancer, depression, clinically significant bleeding, dementia, heart failure, myocardial infarction, physical disability, stroke/TIA.
• Additional measures to those included in the primary and secondary objectives were hemoglobin levels, urine albumin: creatinine ratios, cognitive and physical function, and hospitalizations.
• The study examined whether the potential benefits of low-dose aspirin outweighed the risks in this age group.
• Participants were eligible for the trial if they did not have a current clinical indication for or contraindication (i.e. allergy or increased risk of bleeding) to aspirin, did not have dementia, significant physical disability, low hemoglobin levels, or have a condition that was likely to be fatal during the five years of the trial, and were capable of attending their usual Primary Care Providers (PCPs) clinic and providing informed consent.
• Sample size estimate required 19,000 participants to provide 90% power of a true relative risk benefit of 0.90 for the primary endpoint (a composite of all-cause mortality, incident dementia and persistent physical disability) in an intention-to-treat analysis with an average follow-up of 5 years.
• The trial received financial support from the National Institute on Aging and the National Cancer Institute (NIA and NCI; part of the National Institutes of Health, USA), the National Health and Medical Research Council of Australia, Monash University and the Victorian Cancer Agency.
• Bayer Pharma (Germany) provided in-kind support through the provision of low-dose aspirin and matching placebo and had no other involvement in the trial.
• ASPREE was conducted in community settings.

Download the ASPREE Clinical Trial Protocol