"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 Dr. Raj C. Shah, an associate professor of family medicine with the Rush Alzheimer's Disease Center in Chicago.
Shah served as principal investigator of the ASPREE trial at Rush University Medical Center, which was an enrollment site for the study through the patient-oriented research team of the Rush Alzheimer's Disease Center. Shah also served on the governance of the entire study as a member of its International Steering Committee, and as co-U.S. investigator with Dr. Anne Murray at the Berman Center in Minneapolis, Minnesota.
"The results will have a significant impact on guidelines about aspirin use for prevention and in daily clinical conversations between clinicians and their older, healthy patients regarding whether aspirin should or should not be used for achieving disability-free longevity," said Shah.
Rush helped recruit under-represented groups and reduce barriers to study participationThe international, randomized, double-blind, placebo-controlled trial enrolled 19,114 older people (16,703 in Australia and 2,411 in the United States). Study participants were enrolled at 70 years of age or older, with 65 as the minimum age of entry for African-American and Hispanic individuals in the United States because of their higher risk for dementia and cardiovascular disease. They were followed for an average of 4.7 years to determine outcomes.
Rush researchers provided key national input into the recruitment and retention strategies for participants who are under-represented in aging research, with a special focus on African-American and Hispanic older adults. The Rush team also developed and implemented innovative, in-home assessments to reduce the barriers for continued participation in a study that involved evaluations for up to seven years.
The team of scientists was led by John J. McNeil, MBBS, PhD, head of the Department of Epidemiology and Preventive Health at Monash University, Melbourne, Australia, and Dr. Anne M. Murray, director of the Berman Center for Outcomes and Clinical Research at Hennepin Healthcare in Minneapolis. The research was supported in part by the National Institute on Aging and the National Cancer Institute, both parts of the National Institutes of Health (U01AG029824). The Australian component of the study also received funding from the Australian National Health and Medical Research Council and Monash University. Aspirin and placebo were supplied by Bayer, which had no other involvement with the study.
"Clinical guidelines note the benefits of aspirin for preventing heart attacks and strokes in persons with vascular conditions such as coronary artery disease," said NIA Director Dr. Richard J. Hodes. "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."
Taking aspirin did not affect onset of dementia or physical disabilityIn 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 percent remained alive at the end of the treatment without persistent physical disability or dementia, compared with 90.5 percent 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 percent of participants taking aspirin and 5.2 percent 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.
Aspirin was associated with greater risk of bleedingThe researchers 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 comparably-sized placebo group.
Significant bleeding - a known risk of regular aspirin use - also was measured. The investigators 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 percent) on aspirin and in 265 (2.7 percent) taking the placebo.
As would be expected in an older adult population, cancer was a common cause of death, and 50 percent of the people who died in the trial had some type of cancer. Heart disease and stroke accounted for 19 percent of the deaths, and major bleeding for 5 percent.
"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, associate director for clinical research, National Cancer Institute Division of Cancer Prevention. "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."
Findings do not apply to patients with cardiovascular conditions"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 NIA's Division of Geriatrics and Clinical Gerontology. "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."
As these efforts continue, Hadley emphasized that older adults should follow the advice from their own physicians about daily aspirin use. It is important to note that the new findings do not apply to people with a proven indication for aspirin such as stroke, heart attack or other cardiovascular disease. In addition, the study did not address aspirin's effects in people younger than age 65. Also, since only 11 percent of participants had regularly taken low-dose aspirin prior to entering the study, the implications of ASPREE's findings need further investigation to determine whether healthy older people who have been regularly using aspirin for disease prevention should continue or discontinue use.
McNeil JJ, Woods RL, Nelson MR, Reid CM, Kirpach B, Wolfe R, Storey E, Shah RC, Lockery JE, Tonkin AM, Newman AB, Williamson JD, Margolis KL, Ernst ME, Abhayaratna WP, Stocks N, Fitzgerald SM, Orchard SG, Trevaks RE, Beilin LJ, Donnan GA, Gibbs P, Johnston CI, Ryan J, Radziszewska B, Grimm R, Murray AM; ASPREE Investigator Group.
Effect of Aspirin on Disability-free Survival in the Healthy Elderly.
N Engl J Med. 2018 Sep 16. doi: 10.1056/NEJMoa1800722.
McNeil JJ, Nelson MR, Woods RL, Lockery JE, Wolfe R, Reid CM, Kirpach B, Shah RC, Ives DG, Storey E, Ryan J, Tonkin AM, Newman AB, Williamson JD, Margolis KL, Ernst ME, Abhayaratna WP, Stocks N, Fitzgerald SM, Orchard SG, Trevaks RE, Beilin LJ, Donnan GA, Gibbs P, Johnston CI, Radziszewska B, Grimm R, Murray AM; ASPREE Investigator Group.
Effect of Aspirin on All-Cause Mortality in the Healthy Elderly.
N Engl J Med. 2018 Sep 16. doi: 10.1056/NEJMoa1803955.
McNeil JJ, Wolfe R, Woods RL, Tonkin AM, Donnan GA, Nelson MR, Reid CM, Lockery JE, Kirpach B, Storey E, Shah RC, Williamson JD, Margolis KL, Ernst ME, Abhayaratna WP, Stocks N, Fitzgerald SM, Orchard SG, Trevaks RE, Beilin LJ, Johnston CI, Ryan J, Radziszewska B, Jelinek M, Malik M, Eaton CB, Brauer D, Cloud G, Wood EM, Mahady SE, Satterfield S, Grimm R, Murray AM; ASPREE Investigator Group.
Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly.
N Engl J Med. 2018 Sep 16. doi: 10.1056/NEJMoa1805819.