Aspirin in Reducing Events in the Elderly - ASPREE

Contribution To Literature:

The ASPREE trial showed that aspirin did not prevent disability-free survival, but did increase major bleeding compared with placebo.

Description:

The goal of the trial was to evaluate low-dose aspirin compared with placebo among healthy elderly patients.

Study Design

  • Randomized
  • Parallel
  • Stratified

Healthy elderly patients were randomized to aspirin 100 mg daily (n = 9,525) versus placebo (n = 9,589).

  • Total number of enrollees: 19,114
  • Duration of follow-up: median 4.7 years
  • Median patient age: 74 years
  • Percentage female: 56%
  • Percentage with diabetes: 11%

Inclusion criteria:

  • Healthy individuals ≥70 years of age (or ≥65 years of age for blacks and Hispanics)

Exclusion criteria:

  • Cardiovascular or cerebrovascular disease
  • Dementia
  • High risk of bleeding
  • Contraindication to aspirin

Principal Findings:

The primary outcome, all-cause death, dementia, or physical disability, was 21.5 events per 1,000 person-years in the aspirin group compared with 21.2 events per 1,000 person-years in the placebo group (p = 0.79).

Secondary outcomes:

  • Major hemorrhage: 8.6 events per 1,000 person-years in the aspirin group vs. 6.2 events per 1,000 person-years in the placebo group (p < 0.001)
  • Any intracranial bleeding: 2.5 events per 1,000 person-years in the aspirin group vs. 1.7 events per 1,000 person-years in the placebo group (p < 0.05)
  • Upper gastrointestinal bleeding: 2.1 events per 1,000 person-years in the aspirin group vs. 1.1 events per 1,000 person-years in the placebo group (p < 0.05)
  • Cardiovascular disease (fatal cardiovascular disease, myocardial infarction, stroke, or hospitalization for heart failure): 10.7 events per 1,000 person-years in the aspirin group vs. 11.3 events per 1,000 person-years in the placebo group (p = not significant)
  • All-cause mortality: 5.9% in the aspirin group vs. 5.2% in the placebo group (p < 0.05)
  • Cancer mortality: 3.1% in the aspirin group vs. 2.3% in the placebo group (p < 0.05)

Interpretation:

Among healthy elderly patients, low-dose aspirin therapy was not beneficial. Compared with placebo, aspirin did not improve disability-free survival or reduce major adverse cardiovascular events at a median of 4.7 years. Aspirin was associated with a significant increase in major bleeding, which was attributed to excess intracranial and upper gastrointestinal bleeding. Aspirin was also associated with an increase in all-cause mortality, which was attributed to excess cancer mortality. While the increase in all-cause and cancer mortality is compelling, these findings have not been observed previously and should likely be interpreted with caution.

The ARRIVE trial showed that among younger individuals with moderate risk of coronary heart disease, the use of aspirin was not beneficial.

The ASCEND Aspirin trial showed that among diabetic patients, aspirin reduced the incidence of major adverse cardiovascular events; however, this was somewhat counterbalanced by an increase in major bleeding.

While millions of individuals use aspirin for primary prevention, this routine practice is now questioned in light of recent randomized trial data.

References:

McNeil JJ, Woods RL, Nelson MR, et al., on behalf of the ASPREE Investigator Group. Effect of Aspirin on Disability-free Survival in the Healthy Elderly. N Engl J Med 2018;379:1499-1508.

McNeil JJ, Nelson MR, Woods RL, et al., on behalf of the ASPREE Investigator Group. Effect of Aspirin on All-Cause Mortality in the Healthy Elderly. N Engl J Med 2018;379:1519-28.

McNeil JJ, Wolfe R, Woods RL, et al., on behalf of the ASPREE Investigator Group. Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly. N Engl J Med 2018;379:1509-18.

Editorial: Ridker PM. Should Aspirin Be Used for Primary Prevention in the Post-Statin Era? N Engl J Med 2018;379:1572-4.

Keywords: Anticoagulants, Aspirin, Cardiovascular Diseases, Coronary Disease, Dementia, Diabetes Mellitus, Frail Elderly, Geriatrics, Heart Failure, Hemorrhage, Intracranial Hemorrhages, Myocardial Infarction, Neoplasms, Primary Prevention, Stroke, Vascular Diseases


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