Daily aspirin linked to higher mortality in older adults, study finds

By Dr. Chinta SidharthanFeb 12 2024Reviewed by Susha Cheriyedath, M.Sc.

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

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

Background

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

The primary end-point of the clinical trial was to assess disability-free survival, which essentially included the absence of dementia and other persistent physical disabilities that decreased the lifespan of the individual. The clinical trial reported that there were no significant differences between the treatment and placebo groups in terms of the primary end-points. However, deaths were higher in the aspirin group than in the placebo group. However, the specific causes of the higher mortality rates in the aspirin group had not been investigated.

About the study

In the present 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 time the clinical records were also examined. Any failure to establish contact with the participant, followed by contact with next of kin and examination of health records, was used to identify 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 information from family members. An underlying cause of death was assigned after a thorough examination of this information and using the International Statistical Classification of Diseases Tenth Revision (ICD-10).

The proximal cause of death was also independently established for each mortality case, and cancer-related deaths were tabulated. The data 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. Furthermore, a post-hoc analysis was carried out to explain specific causes of death.

Results

The results reported that the all-cause mortality rate was higher among healthy adults above the age of 70 who were given a 100 mg dose of aspirin every day during the ASPREE trial. Furthermore, the cause of death among these adults was primarily cancer.

Out of the 1052 deaths that occurred in the study, 558 were in the aspirin treatment group. The higher mortality rate in the treatment group as compared to 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 first three years, after which the curves for cancer-related deaths and any-cause mortality were found to diverge for the aspirin group.

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

Furthermore, while aspirin has been known to influence numerous molecular and cellular pathways involved in the development and progression of cancer, as well as metastasis, the biological basis through which aspirin either accelerates or delays cancer remains unclear.

The researchers believe that while the large study population was an advantage in identifying the proximal and underlying causes of mortality, the short follow-up could have prevented the observation of conclusive results on the benefits of aspirin treatment.

Conclusions

Overall, the findings suggested that all-cause mortality and the rate of cancer-related mortality were higher among adults in the ASPREE clinical trial treated with a daily dose of 100 mg aspirin as compared to those in the placebo group. However, these results contrast with previous similar clinical trials, highlighting that these findings should be interpreted with caution.