Daily aspirin linked to higher mortality in elderly, study finds

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

Study: Effect of aspirin on all-cause mortality in healthy elderly. Image credit: fizkes / Shutterstock

Record

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

The primary endpoint of the clinical trial was the assessment of disability-free survival, which essentially included the absence of dementia and other persistent physical disabilities that reduced the person’s lifespan. The clinical trial reported that there were no significant differences between the treatment and placebo groups in terms of the primary endpoints. However, deaths were higher in the aspirin group than in the placebo group. However, the specific causes of the higher death rates in the aspirin group had not been investigated.

About the study

In the present study, the researchers looked at the secondary endpoints, which consisted of events of dementia, physical disability or death. The trial conducted follow-up through quarterly telephone checks and annual in-person visits, during which clinical records were also reviewed. Any failure to contact the participant, followed by contact with next of kin and review of health records, was used to identify death.

After confirmation of the participant’s death, relevant clinical information was obtained from hospitals, clinicians, hospices or nursing homes, with information collected including hospital progress notes, discharge reports, autopsy reports and information from family members. The underlying cause of death was determined after careful review of this information and using the Tenth Revision of the International Statistical Classification of Diseases (ICD-10).

Proximate cause of death was also determined independently for each case of mortality, and cancer-related deaths were tabulated. Data were analyzed and Cox proportional hazards models were used to calculate hazard ratios for cause-specific and all-cause deaths, which were then compared between treatment and placebo groups. In addition, a post hoc analysis was performed to account for specific causes of death.

Results

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

Of the 1052 deaths in the study, 558 were in the aspirin treatment group. The higher mortality rate in the treatment group compared to the placebo group was mainly attributable 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 all-cause mortality differed between groups aspirin.

However, conflicting results have been reported from studies that have analyzed data from other similar prevention clinical trials. These studies have found that continuous aspirin therapy for four to five years demonstrates a protective effect on cancer-related deaths. Metastasis rates among the aspirin-treated groups were also found to be lower compared to the placebo-treated groups.

Furthermore, while aspirin is known to affect numerous molecular and cellular pathways involved in cancer development and progression, as well as metastasis, the biological basis by which aspirin either accelerates or delays cancer remains unclear.

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

conclusions

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