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Day by day aspirin linked to higher mortality in older adults, study finds

In a recent study published within the Latest England Journal of Medicine, a team of researchers, including the team that conducted the Aspirin in Reducing Events within the Elderly (ASPREE) clinical trial, analyzed the preliminary data from the trial to grasp whether a day by day dose of aspirin provided any advantages in increasing the disability-free survival rates in older adults.

Study: Effect of Aspirin on All-Cause Mortality within the Healthy Elderly. Image Credit: fizkes / Shutterstock


The ASPREE trial was conducted between 2010 and 2014 and enrolled greater than 19,000 participants above the age of 70, half of whom received a day by day dose of 100 mg aspirin, while the opposite half received a placebo. This trial investigated whether a day by day aspirin dose would increase the healthy or disability-free lifespan of adults older than 70 years. The participants were recruited from the US and Australia from community settings.

The first end-point of the clinical trial was to evaluate disability-free survival, which essentially included the absence of dementia and other persistent physical disabilities that decreased the lifespan of the person. The clinical trial reported that there have been no significant differences between the treatment and placebo groups when it comes to the first end-points. Nonetheless, deaths were higher within the aspirin group than within the placebo group. Nonetheless, the particular causes of the upper mortality rates within the aspirin group had not been investigated.

Concerning the study

In the current study, the researchers examined the secondary end-point data, which consisted of events of dementia, physical disability, or death. The trial conducted follow-ups through quarterly telephonic check-ups and annual in-person visits, during which period the clinical records were also examined. Any failure to determine contact with the participant, followed by contact with next of kin and examination of health records, was used to discover death.

Upon confirmation of the participant’s death, relevant clinical information was obtained from hospitals, clinicians, hospices, or nursing homes, with the compiled information including progress notes from the hospital, discharge reports, autopsy reports, and knowledge from members of the family. An underlying reason for death was assigned after an intensive examination of this information and using the International Statistical Classification of Diseases Tenth Revision (ICD-10).

The proximal reason for death was also independently established for every mortality case, and cancer-related deaths were tabulated. The information was analyzed, and Cox-proportional hazards models were employed to calculate the hazard ratios for specific cause-related deaths and deaths from any cause, which were then compared between the treatment and placebo groups. Moreover, a post-hoc evaluation was carried out to clarify specific causes of death.


The outcomes reported that the all-cause mortality rate was higher amongst healthy adults above the age of 70 who got a 100 mg dose of aspirin every single day in the course of the ASPREE trial. Moreover, the reason for death amongst these adults was primarily cancer.

Out of the 1052 deaths that occurred within the study, 558 were within the aspirin treatment group. The upper mortality rate within the treatment group as in comparison with the placebo group, was mainly attributed to cancer-related deaths. The incidence curves for cancer-related deaths and all-cause mortality were found to be similar for the aspirin and placebo groups for the primary three years, after which the curves for cancer-related deaths and any-cause mortality were found to diverge for the aspirin group.

Nonetheless, contrasting results have been reported by studies which have meta-analyzed data from other similar prevention clinical trials. Those studies have found that continuous treatment with aspirin for 4 to 5 years exhibits a protective effect on cancer-related deaths. The metastasis rates amongst groups that were treated with aspirin were also found to be lower as in comparison with groups that received the placebo.

Moreover, while aspirin has been known to influence quite a few molecular and cellular pathways involved in the event and progression of cancer, in addition to metastasis, the biological basis through which aspirin either accelerates or delays cancer stays unclear.

The researchers consider that while the big study population was a bonus in identifying the proximal and underlying causes of mortality, the short follow-up could have prevented the commentary of conclusive results on the advantages of aspirin treatment.


Overall, the findings suggested that all-cause mortality and the speed of cancer-related mortality were higher amongst adults within the ASPREE clinical trial treated with a day by day dose of 100 mg aspirin as in comparison with those within the placebo group. Nonetheless, these results contrast with previous similar clinical trials, highlighting that these findings must be interpreted with caution.

Journal reference:

  • McNeil, J. J., Nelson, M. R., Woods, R. L., Lockery, J. E., Wolfe, R., Reid, C. M., Kirpach, B., Shah, R. C., Ives, D. G., Storey, E., Ryan, J., Tonkin, A. M., Newman, A. B., Williamson, J. D., Margolis, K. L., Ernst, M. E., Abhayaratna, W. P., Stocks, N., Fitzgerald, S. M., & Orchard, S. G. (2018). Effect of Aspirin on All-Cause Mortality within the Healthy Elderly. Latest England Journal of Medicine, 379(16), 1519–1528. DOI: 10.1056/NEJMoa1803955,
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