Research has shown the effectiveness of aspirin in the secondary prevention of cardiovascular disease among persons with a history of coronary heart disease. The evidence of primary prevention is less conclusive, despite some studies showing that aspirin reduces the incidence of cardiovascular events and possibly reduces the incidence of cancer and cancer-associated mortality.
In a new study published in the New England Journal of Medicine, scientists conducted a randomized, placebo-controlled trial to determine if the daily use of aspirin prolongs a healthy life span that is defined as being free from dementia and physical disability.
Study: Effect of Aspirin on Disability-free Survival in the Healthy Elderly. Image Credit: fizkes / Shutterstock.com
About the study
In this study, scientists conducted the Aspirin in Reducing Events in the Elderly (ASPREE) randomized, placebo-controlled trial across 34 sites in the United States and 16 sites in Australia. Trial subjects were community-dwelling men and women from Australia and the United States.
A total of 19,114 persons were enrolled in the study, of whom 9,525 were randomly assigned to receive aspirin. The participants were 70 years of age or older (≥65 years of age for blacks and Hispanics in the U.S.) and were free of any chronic illness.
White participants comprised 91% of the study cohort. Additionally, 56.4% of the participants were women and 11.0% reported previous regular aspirin use.
A total dose of 100 mg of enteric-coated aspirin was administered daily to the subjects. The trial was terminated after approximately five years of follow-up (median of 4.7 years). This was done because scientists determined that no further aspirin administration would be beneficial, in terms of the endpoint.
Study findings
The use of aspirin did not differ from the placebo, in terms of influencing the rates of disability-free survival. The median survival rate was found to be 4.7 years.
Scientists found no significant difference between the participants in the U.S. and Australia, or across a range of other subgroups. The findings of the ASPREE trial on Blacks and Hispanics were not clear, owing to their small sample size.
Previous studies on aspirin focused on bringing about a reduction in the incidence of cardiovascular events. In the elderly, long-term use of a preventive drug like aspirin could be justified by the potentially prolonged healthy life span. Scientists caution that endpoint, reflecting this outcome, should consider the costs and benefits associated with the use of a preventive agent.
Aspirin is expected to reduce the incidence of disability from different causes. The mechanism through which aspirin works is by reducing platelet aggregation and thrombotic obstruction.
This reduces the risk of ischemia in the heart and brain; however, chronic aspirin use may put individuals at an increased risk of intracerebral and/or gastrointestinal bleeding. In the current trial, the endpoint of disability-free survival included the costs and benefits mentioned above.
Among all endpoint events, deaths constituted half, dementia accounted for 30%, and physical disability accounted for 20%. The rates of dementia, physical disability, or death did not differ across the two groups. However, owing to the adverse effects of aspirin, scientists further investigated the specific causes of death and published these findings separately.
The incidence of major hemorrhage was higher in the group that received aspirin as compared to the control group. This resulted in an additional 2.4 serious bleeding events per 1000 person-years of exposure.
In this study, the lack of aspirin effect was similar across all baseline subgroups except frailty, where the impact was unclear due to the inconsistent effect of aspirin across three frailty categories. The scientists managed to maintain a relatively high level of adherence to the randomly assigned intervention, despite the challenges of having older participants as trial subjects.
Limitations
One of the limitations of the current study was the short time period of intervention, which made it difficult to estimate the impact of aspirin on diseases that have long latencies like Alzheimer’s disease and cancer. Further, the study does not provide information on whether aspirin could have favorable effects if taken from a younger age and for a longer duration.
There were a low proportion of subjects who used to take low doses of aspirin before the study commenced, which should be considered when interpreting the results. Lastly, this study does not address the question of whether healthy elderly who have been taking aspirin should continue to do so.
Conclusion
Information on the role of aspirin in increasing a healthy independent life span in older persons is limited. This study conducted an ASPREE trial, with predominantly white participants who were 70 years or older and did not have pre-existing chronic illnesses. Over a median follow-up period of 4.7 years, scientists found no differential effects of aspirin in prolonging disability-free survival.
Journal reference:
- McNeil, J. J., Woods, R. L., Nelson, M. R., et al. (2018) Effect of Aspirin on Disability-free Survival in the Healthy Elderly. The New England Journal of Medicine 379;1499-1508. doi:10.1056/NEJMoa1800722.