Low-Dose Aspirin: No Cancer Prevention Benefit & Increased Mortality Risk in Older Adults – ASPREE Trial Update

New research confirms that daily low-dose aspirin does not reduce the incidence of cancer in healthy older adults and may, in fact, increase the risk of cancer-related death. The findings, stemming from an extended follow-up of the landmark Aspirin in Reducing Events in the Elderly (ASPREE) trial, challenge previous assumptions about aspirin’s potential as a cancer preventative.

The ASPREE trial, originally conducted between 2010 and 2014, enrolled 19,114 participants aged 70 or older (or 65 and older for US Black and Latino individuals) who were free of cardiovascular disease, dementia, and significant physical disability. Participants were randomly assigned to receive either 100 mg of aspirin daily or a placebo. Initial results indicated that aspirin did not reduce overall cancer incidence, and even suggested a higher risk of advanced-stage cancer and cancer-related death. The current study, published in January 2026 in JAMA Oncology, provides a longer-term perspective, following participants through 2024.

Over a median follow-up of 8.6 years, researchers analyzed 3,448 incident cancer cases and 1,173 cancer-related deaths. The analysis revealed that low-dose aspirin had no discernible effect on overall cancer incidence (hazard ratio [HR] 0.98; 95% CI 0.92–1.05). This held true regardless of cancer stage or type, including colorectal cancer (HR 1.01; 95% CI 0.84–1.21).

However, a statistically significant increase in cancer-related mortality was observed among those taking aspirin (HR 1.15; 95% CI 1.03–1.29). Cancer death rates were 7.8 per 1,000 person-years in the aspirin group, compared to 6.8 per 1,000 person-years in the placebo group. The researchers attribute this excess mortality to the 35% increased risk observed at the conclusion of the randomized phase of the trial, particularly among those with stage 4 disease.

To investigate whether any lasting effects of aspirin exposure might emerge after treatment stopped, researchers conducted “legacy analyses” on a subset of 14,907 participants who were cancer-free at the end of the initial trial and consented to continued follow-up. During a median post-trial follow-up of 4.3 years, 1,451 new cancer cases and 376 cancer-related deaths occurred. Importantly, the researchers found no evidence of a persistent “legacy effect” of aspirin on either cancer incidence (HR 0.91; 95% CI 0.82–1.01) or cancer-related mortality (HR 1.02; 95% CI 0.83–1.25).

These findings contrast with some earlier research, primarily conducted in middle-aged populations, which suggested that long-term aspirin use might reduce cancer risk, particularly for colorectal cancer, after a decade of use. The ASPREE trial and its follow-up analyses demonstrate that these benefits do not necessarily translate to older adults.

The study authors acknowledge certain limitations, including the relatively short median duration of randomized treatment (4.7 years), the possibility of confounding factors during the observational phase (such as participants independently starting or stopping aspirin use), and the fact that multiple statistical analyses were performed. However, they emphasize the strengths of the study, including its large sample size, double-blind randomized design, rigorous cancer outcome adjudication, and high participant retention rate over the extended follow-up period.

The implications of this research are significant for clinical practice and public health recommendations. The authors conclude that their findings do not support the routine initiation of long-term, low-dose aspirin therapy for cancer prevention in older adults. This aligns with current recommendations against the use of aspirin for primary prevention in this age group. Individualized risk-benefit assessments remain crucial when considering aspirin therapy, particularly given the absence of demonstrated cancer-preventive benefits and the potential for increased cancer-related mortality.

Further research is needed to explore potential delayed effects of aspirin and to better understand how age influences aspirin’s impact on cancer biology. The study highlights the importance of carefully considering the potential harms and benefits of aspirin therapy, especially in the context of an aging population.