Daily Aspirin Risks Outweigh Benefits for Healthy Older Adults


A placebo-controlled study of daily low-dose aspirin found that treatment did not prolong healthy living in older adults. In fact, aspirin use was associated with increased risk of major hemorrhage.

ASPREE trial, aspirin, cardiovascular disease

Raj C. Shah, MD

Credit: Rush Productions Group

A large, placebo-controlled study of daily low-dose aspirin found that this treatment did not extend a healthy, disability-free lifespan for older adults over 5 years.

Secondary analyses of the Aspirin in Reducing Events in the Elderly (ASPREE) trial examined the effects of daily low-dose aspirin on all-cause mortality as well as on cardiovascular events and bleeding. Participants randomized to the treatment arm had higher all-cause mortality and a higher risk of major hemorrhage compared to placebo. Additionally, neither group had a significantly lower risk of cardiovascular disease.

These results will significantly impact guidelines on aspirin use in older, healthy adults said Raj C. Shah, MD, an associate professor of family medicine with the Rush Alzheimer's Disease Center at Rush University Medical Center in Chicago. Shah served as the principal investigator at Rush University Medical Center and as co-US investigator for the study as a whole.

“Older persons are curious about ways to promote a longer life without physical and cognitive disability and often ask their physicians about options with scientific evidence to achieve a shared decision,” Shah said in an interview with MD Magazine®. “The results of the study provide scientific evidence that daily intake of low-dose aspirin in healthy older persons does not extend a healthy life span.”

The ASPREE trial enrolled 19,114 adults at 50 sites in the US and Australia who were 70 years of age or older (or ≥65 in the case of Black Americans and Hispanics in the US, due to their higher risk of cardiovascular disease or dementia) (median age = 74). Participants were not institutionalized and did not have cardiovascular disease, dementia, or disability. They were randomized to receive 100mg of enteric-coated aspirin (n = 9525) or placebo (n = 9589) daily. Follow-ups were conducted for a median of 4.7 years.

The study’s primary endpoint of death, dementia, or physical disability occurred slightly more often in the aspirin group (n = 921; 21.5 events per 1000 person-years) than the placebo group (n = 914; 21.2 events per 1000 person-years). However, the difference between study groups was not significant (hazard ratio [HR], 1.01; 95% confidence interval [CI], .92 to 1.11; P = .79).

The rate of dementia was 6.7 events per 1000 person-years in the aspirin group and 6.9 events per 1000 person-years in the placebo group (HR, .98; 95% CI, .83 to 1.15). Similarly, the difference in the rate of persistent physical disability in aspirin vs placebo was not significant (4.9 vs 5.8 events per 1000 person-years; HR, .85; 95% CI, .70 to 1.03).

When investigators focused on cardiovascular outcomes, they found that participants in the aspirin group had significantly higher rates of major hemorrhage: 8.6 events per 1000 person-years in the aspirin group and 6.2 events per 1000 person-years in the control group (HR, 1.38; 95% CI, 1.18 to 1.62; P <.001). The rate of cardiovascular disease was 10.7 events per 1000 person-years and 11.3 events per 100 person-years, respectively (HR, .95; 95% CI, .83 to 1.08)

“When combined with the results of other aspirin studies in otherwise healthy persons, the findings of ASPREE may change the guidelines for aspirin use in a healthy general population,” said Shah. “Given the known bleeding risk of aspirin, changes in the recommendations may result in reducing the number of older persons who experience serious bleeding episodes.”

The investigators noted that the overall rate of cardiovascular disease among participants was lower than the expected 22.4 events per 1000 person-years. “The observed rate was approximately half this estimate, most likely reflecting the relatively good health of the participant population at recruitment and the declining rate of cardiovascular disease in the two countries over time and across all age groups,” wrote the authors.

While all-cause mortality was higher in the aspirin group, with 1.6 excess deaths per 1000 person-years, cancer was the principal cause of these excess deaths. “Other primary prevention trials of aspirin have not identified similar results, which suggests that the mortality results reported here should be interpreted with caution,” wrote authors of the all-cause mortality analysis.

The authors noted several limitations with the trial, particularly that the limited follow-up period may have cut off the possibility of a preventive effect of aspirin on cancer or Alzheimer disease.

The primary analysis of the ASPREE trial, “Effect of Aspirin on Disability-free Survival in the Healthy Elderly,” was published in the New England Journal of Medicine.

Additional analyses of the ASPREE trial, “Effect of Aspirin on All-Cause Mortality in the Healthy Elderly” and “Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly” were also published in NEJM.

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