According to the findings from the ASPirin in Reducing Events in the Elderly (ASPREE) study, taking a low-dose aspirin daily does not prolong healthy living in older adults.
Aspirin is a well-established therapy for the secondary prevention of cardiovascular events. However, its role in the primary prevention of cardiovascular disease is unclear, especially in older persons, who have an increased risk. Image credit: Steve Buissinne.
ASPREE is an international, randomized, double-blind, placebo-controlled trial that enrolled 19,114 older people: 16,703 in Australia and 2,411 in the United States.
The study began in 2010 and enrolled participants aged 70 and older (or over 65 years of age among African-American and Hispanic individuals in the United States).
At study enrollment, ASPREE participants could not have dementia or a physical disability and had to be free of medical conditions requiring aspirin use. They were followed for an average of 4.7 years to determine outcomes.
“This work is a key milestone in the more than a decade-long engagement in this large-scale clinical trial in the United States and Australia,” said co-author Dr. Raj C. Shah, from the Rush Alzheimer’s Disease Center.
In the total study population, treatment with 100 mg of low-dose aspirin per day did not affect survival free of dementia or disability.
Among the people randomly assigned to take aspirin, 90.3% remained alive at the end of the treatment without persistent physical disability or dementia, compared with 90.5% of those taking a placebo.
Rates of physical disability were similar, and rates of dementia were almost identical in both groups.
The group taking aspirin had an increased risk of death compared to the placebo group: 5.9% of participants taking aspirin and 5.2% taking placebo died during the study. This effect of aspirin has not been noted in previous studies; and caution is needed in interpreting this finding.
The higher death rate in the aspirin-treated group was due primarily to a higher rate of cancer deaths.
A small increase in new cancer cases was reported in the group taking aspirin but the difference could have been due to chance.
Dr. Shah and colleagues also analyzed the ASPREE results to determine whether cardiovascular events took place.
They found that the rates for major cardiovascular events — including coronary heart disease, nonfatal heart attacks, and fatal and nonfatal ischemic stroke — were similar in the aspirin and the placebo groups.
In the aspirin group, 448 people experienced cardiovascular events, compared with 474 people in the placebo group.
Significant bleeding, a known risk of regular aspirin use, was also measured.
The researchers noted that aspirin was associated with a significantly increased risk of bleeding, primarily in the gastrointestinal tract and brain.
Clinically significant bleeding — hemorrhagic stroke, bleeding in the brain, gastrointestinal hemorrhages or hemorrhages at other sites that required transfusion or hospitalization — occurred in 361 people (3.8%) on aspirin and in 265 (2.7%) taking the placebo.
As would be expected in an older adult population, cancer was a common cause of death, and 50% of the people who died in the trial had some type of cancer. Heart disease and stroke accounted for 19% of the deaths and major bleeding for 5%.
“The increase in cancer deaths in study participants in the aspirin group was surprising, given prior studies suggesting aspirin use improved cancer outcomes,” said Dr. Leslie Ford, from the Division of Cancer Prevention at the National Cancer Institute.
“Analysis of all the cancer-related data from the trial is under way and until we have additional data, these findings should be interpreted with caution.”
“Continuing follow-up of the ASPREE participants is crucial, particularly since longer term effects on risks for outcomes such as cancer and dementia may differ from those during the study to date,” said Dr. Evan Hadley, Director of the Division of Geriatrics and Clinical Gerontology at the National Institute on Aging.
“These initial findings will help to clarify the role of aspirin in disease prevention for older adults, but much more needs to be learned. The ASPREE team is continuing to analyze the results of this study and has implemented plans for monitoring participants.”
“Clinical guidelines note the benefits of aspirin for preventing heart attacks and strokes in persons with vascular conditions such as coronary artery disease,” said Dr. Richard J. Hodes, Director of the National Institute on Aging.
“The concern has been uncertainty about whether aspirin is beneficial for otherwise healthy older people without those conditions. This study shows why it is so important to conduct this type of research, so that we can gain a fuller picture of aspirin’s benefits and risks among healthy older persons.”
The results were published in three papers in the New England Journal of Medicine.
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John J. McNeil et al. Effect of Aspirin on Disability-free Survival in the Healthy Elderly. New England Journal of Medicine, published online September 16, 2018; doi: 10.1056/NEJMoa1800722
John J. McNeil et al. Effect of Aspirin on All-Cause Mortality in the Healthy Elderly. New England Journal of Medicine, published online September 16, 2018; doi: 10.1056/NEJMoa1803955
John J. McNeil et al. Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly. New England Journal of Medicine, published online September 16, 2018; doi: 10.1056/NEJMoa1805819
