For seniors, taking aspirin on a daily basis at a standard low dose is not frowned upon. Nor is it all that uncommon.
Millions of seniors (around 65 and older) around the world take 100mg of aspirin per day in the hopes of achieving improved health. Such low dosages are clinically acceptable and considered beneficial for certain health-related circumstances. So, what is the ASPREE trial and why is the safety of aspirin use now being questioned?
ASPREE, which stands for ‘ASPirin in Reducing Events in the Elderly’ is one of the largest studies conducted (1) on the overall effectiveness of low-dose aspirin as a preventative means with the effect of preserving optimum health. ASPREE is funded by the National Institutes of Health (NIH) in the USA, as well as the National Health and Medical Council, Victorian Cancer Agency and Monash University in Australia.
The team of researchers at Monash University in Melbourne, Australia and the Berman Center for Outcomes and Clinical Research in the USA, are in the process of completing a large-scale and comprehensive study, assessing benefits versus risk factors, specifically for senior populations over the age of 65.
One of the primary research questions addressed in the trial is whether the expected benefit of daily aspirin usage in seniors is actually being realised. Findings from this extensive study have been published as three medical papers in the New England Journal of Medicine on 16 September 2018:
- Effect of Aspirin on All-Cause Mortality in the Healthy Elderly (2)
- Effect of Aspirin on Disability-free Survival in the Healthy Elderly (3)
- Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly (4)
Each paper addresses important questions regarding the primary reasons aspirin is used in order to determine an actual positive or negative outcome. Proposed benefits of aspirin use include the promotion of overall optimum health, reduced risk of the development of serious conditions, such as cardiovascular events like heart attack or stroke, and cancer, dementia, and depression and thereby lower associated mortality.
These are some of main reasons why aspirin is a popular therapy, taken at low, regular dosages (often daily) in older generations, with the belief that the medication promotes longevity and a longer, heathier life. With seniors often falling into high-risk population categories, assessing the safety and actual beneficial outcomes of aspirin usage is necessary, even though it has been reasonably well-established that taking low-doses can be therapeutically useful – particularly for middle-age individuals.
There are still question-marks when it comes to the medication’s ability to reduce instances of cardiovascular risks, intellectual degeneration or decline and certain forms of cancer – especially so in older generations.
As with any pharmacological therapy, weighing up risks versus benefits is an imperative part of the diagnostic / treatment process. Can aspirin use be offset by certain side-effects even though some benefit may be achieved in senior populations? Are the elderly more prone to adverse effects like internal bleeding (something that is known to occur, in general, with this type of medication use)? Can healthy individuals benefit from aspirin use, achieving longer disability-free life expectancies?
ASPREE recruited more than 19 114 Australian and American participants between 2009 / 2010 and 2017, collating initial findings earlier this year in order to try and answer these questions. The estimated completion date for the full analysis is set for January 2019.
Participants selected for the study ranged in age from 65 years upwards, and had not been diagnosed with cardiovascular diseases, disabilities or dementia. Between early 2010 and 2014, participants were divided to receive daily dosages (100 mg) of either enteric-coated aspirin or a placebo. The number of participants in the randomly selected aspirin group totalled 9 525, with the remaining 9 589 receiving the placebo.
The number of female participants were tallied at 56% and only around 11% had used aspirin before on a regular basis.
Can aspirin reduce the risk of ‘all-cause mortality’?
In the first published paper, the team set out to assess whether daily low-dose aspirin usage could indeed help to achieve a longer, healthier and disability-free lifespan in senior populations.
The research identified two ‘end-points’ for their analysis – primary (i.e. disability-free survival) and secondary (i.e. death). During the four-year period, the team recorded a total of 1 052 deaths among the participants. Deaths were categorised by their underlying cause and compared according to the medication group (i.e. enteric-coated aspirin vs. placebo group recipients) in which participants were taking part. The team analysed the identified causes of death in the recorded participants and determined hazard ratios in order to make comparisons between the two medication groups.
The overall finding was that aspirin did not appear to provide a great enough benefit with regards to the primary end-point in older individuals (i.e. disability-free survival), and by extension, the secondary end-point too. The team observed that the secondary end-point in the participants who had taken aspirin before their demise was numerically higher, albeit only slightly, than those who participated in the placebo group – regardless of the cause of death.
Of those who had participated in the aspirin group, the main cause of death was attributed to cancer (3.1%). Approximately 2.3% of those who died from cancer had been placebo group participants.
Although the differences between the groups were marginal, the team surmised that taking aspirin daily as a means to improve overall health, reducing risk for the development of serious diseases (particularly cardiovascular conditions and cancer) was not necessarily all that helpful in older generations. The team admits that this was an unexpected result as their findings do, to some degree, contradict previous research. Thus, the team recommends that their findings be interpreted within the context of their study design.
Does aspirin promote ‘disability-free survival’?
As part of the quest to live longer and healthier, the consumption of low-dose daily aspirin during the later years has been associated with improving an individual’s life span. For the most part, research in this regard is considered limited and not entirely clear. Although millions of seniors take aspirin for this reason, the question is whether or not such therapy is even beneficial at all.
The research team approached the question with an assessment of whether 5 years of daily therapy could extend a generally healthy senior person’s life span, as well as whether or not his / her quality of life could predominantly be disability-free (i.e. not affected by illness or medical impairment).
During the same period of assessment and using the same participant groupings, in this evaluation the primary end-point was characterised by persistent physical disability, dementia or a composite of death. The secondary end-point assessed any primary end-point components applicable to an individual and the possibility of a major bleeding (haemorrhage) event.
The assessment was concluded after around 4.7 years of follow-up (under the original 5-year period). It was identified that during this period, little to no benefit could be absolutely linked with regular or continuous use of low-dose aspirin – in terms of the primary end-points. Thus, the medication may not be all that useful in extending a generally healthy person’s lifespan after all.
Secondary end-point findings also showed that major bleeding events were higher in participants taking aspirin than the placebo group – 3.8% and 2.8% respectively. Thus, the team concluded that low-dose aspirin use over a 5-year period may also lead to elevated risk of bleeding internally.
Is aspirin a preventative therapy for cardiovascular events?
For many individuals deemed as being at risk of possible cardiovascular events, regular low-dose aspirin use is often recommended. Medical professionals generally recommend use in a secondary prevention capacity. The research team explored whether any primary prevention benefit in older individuals could be applicable, particularly those deemed as being high risk for these types of events. To date, research in this regard is limited and findings not entirely clear.
Primary end-points again looked at persistent physical disability, dementia and composites of death. Secondary end-points factored in major internal bleeding events and cardiovascular disease, which was defined by conditions such as fatal and non-fatal coronary heart disease or heart attack, fatal and non-fatal stroke events or hospitalisations for heart related conditions, including failure.
Findings after the 4.7-year assessment established that within the aspirin group, 10.7 cardiovascular events per 1 000 individuals occurred. By comparison, the rate was 11.3 events per 1 000 individuals in the placebo group. Major bleeding events occurred at a rate of 8.6 events per 1 000 individuals in the aspirin group and an average of 6.2 per 1 000 in the placebo group.
Once again, it appeared that risk of major haemorrhage (bleeding) was a higher in the aspirin group. This, the team surmised, meant that aspirin therapy as a primary preventative measure could not safely be implemented in older adults. As such, this also means that the risk of cardiovascular conditions could also not be sufficiently lowered with low-dose aspirin use.
Should guidelines for aspirin therapy in seniors be re-assessed?
This study was designed on a large scale, although mostly observational, and assessed daily low-dose aspirin use in a comprehensive manner. It is also one of the few studies geared towards establishing whether primary and secondary benefits could outweigh the potential risks in older persons using this relatively inexpensive medication. Millions worldwide are using this medication, for various reasons. Are they placing themselves at higher risk of complications they are already vulnerable to? This study appears to answer the question in the affirmative.
To date, regular low-dose aspirin has been recommended to adults between the ages of 50 and 60 (with a 10% or higher risk of cardiovascular illness) as a primary preventative therapy. An increased risk of bleeding is generally not considered clinically significant. As such many, within this age group typically implement daily therapy over at least a 10-year period in order to gain the perceived overall health benefit.
For individuals aged between 60 and 70, this kind of recommendation is often personalised to a person’s specific physical condition, and haemorrhage risk becomes a deciding factor. In general, the risk of internal bleeding increases as we age. Should a person within this age group be considered to be at low-risk for the development of bleeding, regular low-dosage therapy may be considered. From 70 onwards, evidence has been somewhat sketchy. It is expected that haemorrhage risk may be increased, and yet clinical research comparing benefit over risk is limited. This study not only looked at one of the greatest risks – that of bleeding – it also assessed the overall benefit of aspirin usage, and the outcome does not appear to be in favour of its use.
As such, general practice may need to reassess acceptable aspirin use among senior populations. The reality is, many are using the medication fairly frequently.
Monash University’s Department of Epidemiology and Preventative Medicine head, Professor John McNeil agrees that global guidelines of use do require revision, as well as more refined research when it comes to senior specific age-groups. Aspirin is widely used (and has been for over a century) and yet, its use as a preventative means in these populations is still not entirely clear.
“These findings will help inform prescribing doctors who have long been uncertain about whether to recommend aspirin usage to healthy patients who do not have a clear medical reason for doing so,” he says.
This research team is yet to release more of their full study findings and they are still active in a follow-up phase of the study. So far, it is their view that an aspirin-a-day should not be used in an attempt to prolong health or increase one’s life span, and nor is it significantly useful for primary preventative treatment. Aspirin may not help to lower a person’s risk of conditions which are commonly associated with aging populations. The blood thinning and anti-inflammatory properties of aspirin won’t necessarily prevent the development of disabling medical conditions. This means that millions who don’t have an existing medical reason to be taking aspirin are unnecessarily taking the drug and placing themselves at risk of unnecessary complications, and potentially serious ones at that.
Regular use may elevate risk for major bleeding occurrences (particularly in the gastrointestinal tract or brain), which most aging population groups are more susceptible to anyway. Taking aspirin will not provide enough benefit to nullify this risk.
The research team, however, does not necessarily caution medical professionals not to recommend aspirin therapy where there is a specific reason to do so. Patients on aspirin therapy as recommended by a medical professional (i.e. those who have a medical reason to take it) should also not necessarily feel the need to discontinue treatment for fear of falling ill. A previously experienced cardiovascular event may warrant this type of treatment and in this sense, secondary prevention may be beneficial – with careful medical monitoring regarding elevated risk factors. Any concerned patients should consult their doctors before abruptly discontinuing treatment.
These research findings aside, aspirin is still generally regarded as relatively safe to use. Until such time as further research can determine more detail regarding use in aging populations, this team appears to agree that more care in recommending regular treatment should be considered. Long-term benefits verses risk still need to be clinically assessed in greater depth.
References:
1. ClinicalTrials.Gov. 24 December 2009. Aspirin in Reducing Events in the Elderly (ASPREE): https://clinicaltrials.gov/ct2/show/NCT01038583 [Accessed 18.09.2018]
2. The New England Journal of Medicine. 16 September 2018. Effect of Aspirin on All-Cause Mortality in the Healthy Elderly: https://www.nejm.org/doi/full/10.1056/NEJMoa1803955?query=main_nav_lg [Accessed 18.09.2018]
3. The New England Journal of Medicine. 16 September 2018. Effect of Aspirin on Disability-free Survival in the Healthy Elderly: https://www.nejm.org/doi/full/10.1056/NEJMoa1800722?query=main_nav_lg [Accessed 18.09.2018]
4. The New England Journal of Medicine. 16 September 2018. Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly: https://www.nejm.org/doi/full/10.1056/NEJMoa1805819?query=main_nav_lg [Accessed 18.09.2018]