The hypothesis that low-dose aspirin might eventually lower cancer risk after years of use appears unsupported in adults aged 70 years or older, according to new long-term data from the ASPREE trial.

Over a median follow-up of 8.6 years, daily 100-mg aspirin was not associated with reduced cancer incidence and was associated with a higher risk for cancer-related death, lead author Suzanne G. Orchard, PhD, of Monash University, Melbourne, Australia, and colleagues, reported. The increased risk for cancer-related mortality was driven by deaths during the randomized treatment period.

These findings, published in JAMA Oncology, suggest that the protective benefits of aspirin seen in younger populations do not translate to adults older than 70 years.

“You can stick a fork in aspirin for primary prevention in the elderly — it’s done,” H. Gilbert Welch, MD, of the Center for Surgery and Public Health at Brigham and Women’s Hospital, Boston, told Medscape Medical News. “I say this having worked hard to start all my patients on aspirin in the 1990s. Then it was to prevent cardiovascular disease; now it is to prevent cancer. The reality seems to be that it causes more problems than it solves.”

How Do These Data Build on Previous ASPREE Findings?

ASPREE (Aspirin in Reducing Events in the Elderly) was a randomized clinical trial that enrolled participants between 2010 and 2014, with randomized treatment continuing until 2017, in Australia and the US. Individuals aged 70 years or older (65 years or older among Black and Hispanic patients in the US) without dementia, disability, or cardiovascular disease were assigned to receive either daily 100-mg aspirin or a placebo.

In 2018, the primary ASPREE analysis of 19,114 older adults reported that aspirin was associated with higher all-cause mortality, driven primarily by an increase in cancer-related deaths. The authors noted that these findings conflicted with previous primary prevention trials of aspirin and called for cautious interpretation.

A more recent secondary analysis from 2025 sought to determine if aspirin might still prevent cancer in specific ASPREE subgroups. With a median follow-up of 4.5 years, the dataset included 9350 older adults from the trial. Indeed, the investigators reported “significant heterogeneity” in cancer prevention benefit among aspirin users, with the greatest benefit detected among individuals with clonal hematopoiesis of indeterminate potential (CHIP).

In response, however, Welch previously called this “personalized medicine run amok.” He noted the impracticality of conducting DNA-based liquid biopsies on all older patients to identify those with CHIP and suggested that such findings distract from the more concerning risk for cancer death.

Why Was the Present ASPREE Analysis Conducted?

Although the 2018 analysis reported no cancer prevention benefit from aspirin alongside a higher risk for cancer-related death, there remained the possibility of a delayed benefit, which has been observed in trials of middle-aged individuals. This “legacy effect” may not appear until many years after treatment begins.

For example, the Women’s Health Study, which involved women with a mean age of 55 years, found no cancer benefit during the 10-year active treatment period. But then, 16 years after the intervention period, a 42% reduction in colorectal cancer incidence emerged during extended posttrial follow-up in the aspirin group. Similarly, a meta-analysis of other trials suggested that aspirin’s protective effect against cancer death typically becomes evident only after more than 4 years of continuous therapy.

The new study addresses this possibility by combining the original 4.7-year randomized trial period with the observational ASPREE-XT extension study, yielding a median of 8.6 years of follow-up.

What Were the Key Findings From the Most Recent ASPREE Analysis?

The new analysis included the same 19,114 individuals from the 2018 analysis. Across the trial and posttrial follow-up period, 3448 incident cancers and 1173 cancer-related deaths occurred.

No evidence of a delayed legacy effect was detected.

Specifically, the extended follow-up showed no statistically significant reduction in cancer incidence among those originally assigned to aspirin.

The risk for cancer-related death was significantly more common among those who took aspirin during the trial (hazard ratio [HR], 1.15; 95% CI, 1.03-1.29). Of note, however, this difference was driven by cancer-related deaths that occurred during the trial period and not due to cancer-related deaths that occurred after aspirin exposure ended. In the post-randomization observational phase, the original aspirin assignment was not associated with increased cancer mortality (HR, 1.02; 95% CI, 0.83-1.25).

No statistically significant treatment-effect heterogeneity was detected across prespecified subgroups.

Why Is There a Discrepancy Between Age Groups?

“The key takeaway is that aspirin’s effects seem to depend on when it’s started,” Mohamed E. Abazeed, MD, PhD, professor and chair of radiation oncology at Northwestern University Feinberg School of Medicine, Chicago, told Medscape Medical News. “What may help in younger people does not automatically translate into benefit for older adults.”

Orchard and colleagues suggested that the biology of aging may alter how aspirin affects cancer risk.

“In older adults…age-related declines in immune function (immunosenescence) and age-related low-grade chronic inflammation (inflammaging) may attenuate aspirin’s anti-tumoral effects,” the investigators wrote.

Mary Beth Terry, PhD, professor of epidemiology at Columbia University Irving Medical Center, New York City, agreed, noting that cancer risk factors, and therefore preventive strategies, may shift with age.

“Later-onset cancers diagnosed in the elderly are similar to other later-onset chronic diseases where risk and preventive factors that predict risk at early ages may not predict risk at later ages,” Terry told Medscape Medical News. “Similarly, when we see an absence of risk factors mapping to later-onset cancers, it does not mean that those same factors are not important for earlier-onset cancers.”

How Might These Findings Affect Clinical Practice?

Orchard and colleagues concluded that initiating a multiyear aspirin strategy for cancer prevention is not recommended in older adults.

This reinforces the 2022 US Preventive Services Task Force update, which recommended against initiating aspirin for primary prevention in adults aged 60 years or older.

“Based on these findings, for most older adults, aspirin should not be taken solely to prevent cancer,” Abazeed said. “Decisions about aspirin use should be individualized and discussed with a healthcare provider, weighing cardiovascular benefits against bleeding and other risks.”

Welch noted that while the primary prevention door is closing, other indications remain valid.

“[It’s] always good to remind your readers of the value of aspirin in the acute setting, particularly acute coronary syndrome,” he said.

The ASPREE and ASPREE-XT studies were supported by the National Institute on Aging and the National Cancer Institute at the National Institutes of Health (NIH), by the National Health and Medical Research Council of Australia, and by Monash University and the Victorian Cancer Agency. Bayer AG provided the study drug but had no other role in the study. Abazeed reported receiving funding from Varian Medical Systems and NIH. Orchard reported receiving grants from the NIH and National Cancer Institute. Welch and Terry reported having no relevant financial relationships.