When Evidence Changes Practice: Rethinking Aspirin in Older Adults

Most people want to live long, healthy lives and age well. As a geriatrician, a doctor specializing in the care of older persons, Anne Murray, MD, MSc, has pursued research to help patients achieve a healthy lifespan, or an independent life without dementia or disability.

Dr. Murray is an internal medicine doctor and geriatrician at Hennepin Healthcare. She is also a dementia epidemiologist, studying how commonly different types of dementia and cognitive impairment (CI) occur in different populations and their risk factors to better understand how to prevent them. She is also Professor of Medicine and an Adjunct Professor of Neurology at the University of Minnesota, and the Medical Director of Hennepin Healthcare Research Institute’s (HHRI’s) Berman Center for Outcomes and Clinical Research (Berman Center).

Dr. Murray co-directed an aspirin study called ASPirin in Reducing Events in the Elderly (ASPREE), with collaborators at Monash University in Melbourne, Australia. The goals of ASPREE were to determine whether daily low-dose aspirin (LDA) might preserve a healthy lifespan or reduce the risk of cardiovascular disease (CVD), and to identify other factors that might prolong healthy lifespan.

The ASPREE study examined whether LDA could prolong a healthy lifespan, free of dementia and disability.

Previous clinical trials using aspirin as secondary prevention to treat people who already had at least one previous heart attack or stroke showed that aspirin or a blood thinner was effective in reducing the risk of a recurrent heart attack or stroke.

However, despite the lack of strong evidence that aspirin is effective in primary prevention, both the American College of Cardiology (ACC) and U.S. Preventive Services Task Force (USPSTF) international guidelines previously supported daily low-dose aspirin use to prevent first-time strokes or heart attacks for men older than 45 and women older than 55.

“However, many people were prescribed preventive aspirin because of their strong family history and not necessarily because they had a cardiovascular event.” It raised the question of whether taking aspirin was harmful or helpful as primary prevention against a first heart attack or stroke, said Murray.

To pursue this question further, the 2010-2017 ASPREE Clinical Trial was conducted across 30 sites across the United States and in Australia in more than 19,000 healthy adults over 65 with no prior dementia, physical disability, or cardiovascular disease, to determine if LDA (100 mg) could extend disability-free survival. They also examined whether a daily LDA decreased the occurrences of cognitive decline, cardiovascular disease, physical disability, cancer, depression, and major bleeding episodes.

Results of the ASPREE study, published in three articles in the New England Journal of Medicine (NEJM) in September 2018, showed that aspirin was not effective in prolonging healthy lifespan, or as a primary preventive measure against the individual outcomes of dementia, death, disability, cardiovascular disease, or stroke. These findings led to updated aspirin guidelines for the American College of Cardiology/American Heart Association in March 2019 and the USPTFS guidelines, advising against daily low- dose aspirin for the prevention of heart attack and stroke.

In addition, the study found that taking a daily aspirin increased the risk of gastrointestinal (GI) bleeding by about 38%, a 13% overall increased risk of death, and an earlier death from cancer.

“Subsequent analysis suggests that this increased death risk is most likely from metastatic cancer and associated bleeding. But we are pursuing genomic studies in those patients who have cancer tissue, as the cause may have been related to the genomics of their cancer and their microbiome, and its interaction with aspirin. The cancer result was a big surprise [because] previous studies have suggested there may be a protective effect against colon cancer in people who took [a slightly higher dose] of daily aspirin,” said Murray.

Aspirin is still recommended for some patients with a previous history of CVD or stroke as an effective secondary prevention (although other newer blood thinner medications are often recommended). However, people 65 and older without a history of heart attack, stroke, or atrial fibrillation, or heart valve disease should not be taking aspirin to prevent these events or prolong a healthy lifespan.

The ASPREE study has also led to more than 18 sub-studies to explore specific health questions that weren’t included in the original 2010-2017 ASPREE study, such as the  Biobank, HEARING, ASPREE-Depression, ASPREE-G (Genomics) studies, as well as the ASPREE Longitudinal Study of Older Persons (ALSOP) medical and social survey.

ASPREE Sub-Study: ASPREE – eXTension (ASPREE-XT): 2017-ongoing

The ASPREE-XT study is one of the first large-scale observational studies in older adults. The study examines the long-term health outcomes of participants previously randomized to aspirin and who have now discontinued use. Its second aim is to investigate the lifestyle and other risk factors that may be predictors of age-related diseases or healthy longevity. The ASPREE-XT Microbiome sub-study has also collected stool samples to measure the role of the microbiome and genomics in the risk of colon cancer in relation to aspirin.

The findings in ASPREE-XT so far have continued to confirm the results from the initial ASPREE study. The long-term delayed effect of low-dose aspirin did not promote healthy longevity when used as a primary prevention method for reducing dementia or physical disability. It also did not prevent cardiovascular disease (heart attack or stroke) and was still associated with a small increased risk of death.

ASPREE Sub-Study: ASPREE Long-Term (ASPREE-LT): 2026 - ongoing

ASPREE-LT is the next follow-up observational study of ASPREE, funded by a recent grant from the National Cancer Institute (NCI) at the National Institutes of Health (NIH) to follow previous ASPREE participants for another five years, creating a 15+ year longitudinal study. A critical study goal of this long-term follow-up is to provide new data to the USPSTF, one of the world’s largest guideline committees, as they need additional data from clinical trials lasting more than 10 years, to determine the benefits versus risks of taking low-dose aspirin for colorectal cancer prevention in people over age 70.

The study will continue to follow the former ASPREE-XT participants (now an average of 85 years old) via phone contact over the next 4 years annually to collect their health information, including cancer diagnosis, to determine whether there is a long-term effect from taking aspirin as a primary cancer prevention strategy.

The ASPREE clinical trial and its sub-studies have been landmark studies, disproving long-held beliefs and aspirin guidelines in medical practices.

“It takes a long time to change medical practice that's been so entrenched, especially among older populations who don't like to change routines when they feel like they've been doing the right thing, and especially among providers who may not be as informed regarding the new changes or be convinced of the findings. Scientists have an obligation to improve public health by publishing results of their studies that challenge previous beliefs, so that health care providers and patients can benefit from these new findings,” said Murray.

Related Resources:

WebMD article - "These 7 Aspirin Myths Won't Die"

• An evidence‑based overview that debunks common misconceptions about daily aspirin use and explains what current research really shows.

Minnesota Good Age magazine - "Top Doctor: Dr. Anne Murray"

• A profile of geriatrician and researcher Dr. Anne Murray, highlighting her career‑long impact on aging, dementia, and kidney disease research.

Berman Center for Outcomes & Clinical Research (HHRI)

• A global clinical research center leading large‑scale studies to improve care for chronic diseases, aging, dementia, and kidney disease.

Hennepin Healthcare - Geriatric Medicine

• A clinical program dedicated to comprehensive, patient‑centered care for older adults, addressing complex medical and cognitive needs.

Healthy Aging Through the Senior Years (HATS) Study

• A community‑based research study examining brain health and dementia risk in older Black adults to advance health equity in aging research.