Low-Dose Aspirin Fails to Prevent Cancer, May Increase Mortality in Older Adults: Landmark Study
A long-term follow-up of the ASPREE trial reveals that daily low-dose aspirin does not reduce cancer incidence in older adults and is, in fact, linked to a heightened risk of cancer-related death, challenging previous assumptions about its preventative benefits.
The original Aspirin in Reducing Events in the Elderly (ASPREE) trial, a rigorous randomized clinical trial, initially enrolled 19,114 participants from Australia and the United States aged 70 and older – or 65 and older for US Black and Latino individuals – who were healthy at the study’s outset. Participants were assigned to receive either 100 mg of aspirin daily or a placebo between 2010 and 2014, with a median treatment duration of 4.7 years. Researchers continued to observe the participants through an extension study, ASPREE-XT, until 2024, to assess long-term effects.
While earlier research, primarily focused on middle-aged individuals, suggested a potential protective effect of aspirin against cancer, particularly colorectal cancer, the ASPREE trial demonstrated no impact on overall cancer incidence with low-dose aspirin. Instead, the study found an increased risk of late-stage cancer diagnoses and a concerning rise in cancer-related mortality.
Long-Term Follow-Up Confirms Initial Findings
Published in JAMA Oncology, the extended follow-up examined cancer incidence and mortality over a 10-year period (median 8.6 years) and investigated whether any “legacy effects” remained after participants stopped taking aspirin. Over the combined randomized and post-randomized phases, researchers documented 3,448 incident cancers and 1,173 cancer-related deaths.
The data showed no association between low-dose aspirin and overall cancer incidence (hazard ratio [HR] 0.98; 95% CI 0.92–1.05), nor did it affect cancer incidence based on stage or type, including colorectal cancer (HR 1.01; 95% CI 0.84–1.21). Incidence rates remained consistent across localized, metastatic, hematological, and solid tumors.
However, a significant finding emerged: aspirin was associated with a 15% increase in cancer-related mortality over the long-term follow-up (HR 1.15; 95% CI 1.03–1.29). Cancer death rates were 7.8 events per 1,000 person-years in the aspirin group compared to 6.8 events per 1,000 person-years in the placebo group. “This excess mortality likely reflected the 35% increased risk observed at the end of the randomized phase, particularly driven by stage 4 disease,” researchers noted.
No Evidence of Lasting Protective Effects
Legacy analyses were conducted on 14,907 participants who were cancer-free at the trial’s conclusion and agreed to continued follow-up. During the post-trial period (median 4.3 years), 1,451 new cancers were diagnosed and 376 cancer-related deaths occurred.
Crucially, the initial assignment to aspirin or placebo did not influence cancer incidence (HR 0.91; 95% CI 0.82–1.01) or cancer-related mortality (HR 1.02; 95% CI 0.83–1.25), indicating no persistent protective effect after treatment ceased.
The study authors acknowledged certain limitations, including the relatively short duration of randomized treatment, the possibility of confounding factors during the observational phase – such as participants independently using aspirin – and the use of multiple analyses without adjustments for multiplicity.
Despite these limitations, the study’s strengths are considerable: a large sample size, a double-blind randomized controlled trial (RCT) design, rigorous evaluation of cancer outcomes, and high participant retention over the extended follow-up period.
The authors concluded that their findings do not support initiating long-term, low-dose aspirin therapy for cancer prevention in older adults. They emphasized the need for further research with longer follow-up periods to explore potential delayed effects and to better understand how age influences aspirin’s impact on cancer biology.
Reference: Orchard S G et al. Cancer Incidence and Mortality With Aspirin in Older Adults: Follow-Up of the ASPREE Trial. JAMA Oncol 2026 Jan 29:e256196.
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