Low-Dose Aspirin Increases Cancer Mortality Without Reducing Cancer Incidence in Older Adults: JAMA

This binational community-based cohort study included older adults from Australia and the United States who were originally recruited into the ASPREE randomized clinical trial between 2010 and 2017. Participants were community-dwelling individuals aged 70 years or older, or 65 years or older for US minority participants, who were free from overt cardiovascular disease, dementia, or physical disability that limits independence at baseline. The observational extension phase, ASPREE-XT, recruited participants from 2018 to 2024.

The present analysis has long-term follow-up data from 2010 to 2022, and the analysis of the data was done between May and November 2025. A total of 19,114 older participants were included in the study, with a mean age of 75.1 years (standard deviation of 4.5 years), and 56.4% were female. The participants were randomly assigned to take either 100 mg of aspirin or placebo each day.

Key findings

• Over 10 years of follow-up, with a median of 8.6 years (interquartile range 7.4 to 10.0 years), 3,448 new cases of cancer and 1,173 cancer deaths were ascertained in ASPREE and the extension phase.

• Low-dose aspirin did not reduce the incidence of cancer overall, with a hazard ratio of 0.98 (95% confidence interval 0.92 to 1.05).

• There were no significant associations according to stage at diagnosis or type of cancer, including colorectal cancer, for which the hazard ratio was 1.01 (95% confidence interval 0.84 to 1.21).

• Although there was no effect on cancer incidence, low-dose aspirin was associated with a statistically significant increase in cancer-related mortality, with a hazard ratio of 1.15 (95% confidence interval 1.03 to 1.29).

• This corresponds to a 15% excess risk of death from cancer in aspirin users over the total trial and follow-up period.

• To assess potential legacy effects, researchers studied 14,907 participants who were cancer-free during the randomized trial and were subsequently enrolled in ASPREE-XT. The median age of this subgroup was 78.6 years (interquartile range 76.2 to 82.1 years), and 57.5% were female.

• During the post-trial period, 1,451 incident cancers and 376 cancer deaths occurred. In the observational phase, there were no differences in cancer incidence (hazard ratio 0.91; 95% confidence interval 0.82 to 1.01) or cancer-related mortality (hazard ratio 1.02; 95% confidence interval 0.83 to 1.25) in those previously assigned aspirin compared with placebo, indicating that the observed increase in mortality during the trial was not sustained after stopping therapy.

During a median follow-up of 8.6 years, low-dose aspirin did not show any benefit in lowering the incidence of cancer in older adults but was associated with a significantly higher risk of death due to cancer during active treatment. There was no legacy effect seen after the end of the treatment, as the risk of cancer incidence and death was not influenced by aspirin use in the previous trial in the post-trial period. These results suggest that the use of low-dose aspirin for cancer prevention in adults aged 70 years or older is not recommended and could be harmful.

Reference:

Orchard SG, Polekhina G, Zalcberg J, et al. Cancer Incidence and Mortality With Aspirin in Older Adults: Follow-Up of the ASPREE Trial. JAMA Oncol. Published online January 29, 2026. doi:10.1001/jamaoncol.2025.6196