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Clinician Article

Effect of Aspirin on Disability-free Survival in the Healthy Elderly.



  • McNeil JJ
  • Woods RL
  • Nelson MR
  • Reid CM
  • Kirpach B
  • Wolfe R, et al.
N Engl J Med. 2018 Oct 18;379(16):1499-1508. doi: 10.1056/NEJMoa1800722. Epub 2018 Sep 16. (Original)

Disciplines
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 7/7
    Newsworthiness - 7/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 7/7
    Newsworthiness - 7/7
  • Internal Medicine
    Relevance - 7/7
    Newsworthiness - 5/7
  • Neurology
    Relevance - 6/7
    Newsworthiness - 7/7
  • Public Health
    Relevance - 6/7
    Newsworthiness - 6/7
  • Geriatrics
    Relevance - 6/7
    Newsworthiness - 5/7

Abstract

BACKGROUND: Information on the use of aspirin to increase healthy independent life span in older persons is limited. Whether 5 years of daily low-dose aspirin therapy would extend disability-free life in healthy seniors is unclear.

METHODS: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or =65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or physical disability. Participants were randomly assigned to receive 100 mg per day of enteric-coated aspirin or placebo orally. The primary end point was a composite of death, dementia, or persistent physical disability. Secondary end points reported in this article included the individual components of the primary end point and major hemorrhage.

RESULTS: A total of 19,114 persons with a median age of 74 years were enrolled, of whom 9525 were randomly assigned to receive aspirin and 9589 to receive placebo. A total of 56.4% of the participants were women, 8.7% were nonwhite, and 11.0% reported previous regular aspirin use. The trial was terminated at a median of 4.7 years of follow-up after a determination was made that there would be no benefit with continued aspirin use with regard to the primary end point. The rate of the composite of death, dementia, or persistent physical disability was 21.5 events per 1000 person-years in the aspirin group and 21.2 per 1000 person-years in the placebo group (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11; P=0.79). The rate of adherence to the assigned intervention was 62.1% in the aspirin group and 64.1% in the placebo group in the final year of trial participation. Differences between the aspirin group and the placebo group were not substantial with regard to the secondary individual end points of death from any cause (12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group), dementia, or persistent physical disability. The rate of major hemorrhage was higher in the aspirin group than in the placebo group (3.8% vs. 2.8%; hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P<0.001).

CONCLUSIONS: Aspirin use in healthy elderly persons did not prolong disability-free survival over a period of 5 years but led to a higher rate of major hemorrhage than placebo. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583 .).


Clinical Comments

Family Medicine (FM)/General Practice (GP)

This trial used 100-mg enteric coated aspirin. I wonder whether there might be more benefit with 81-mg chewable aspirin (and less harm).

General Internal Medicine-Primary Care(US)

This study identifies the lack of effectiveness of low-dose aspirin to reduce the primary outcome in elderly patients without cardiovascular disease, dementia, or physical disability. The clinically meaningful and statistically significant increase in major bleeding and hemorrhagic strokes should drive clinicians to discourage patients like the ones included in this trial from starting low-dose aspirin.

Internal Medicine

Not too different from previous information. Important to emphasize the toxicity of aspirin in the elderly, but mostly these seem to be GI bleeds. Missing (or at least I didn't see it) information on other secondary endpoints of importance, such as MI, CVA, or other thrombosis. It seemed that there might end up being a benefit in persistent physical disability, which could be an effect on stroke, but obviously we are unsure. Timeline is too limited to see a beneficial effect on cancer incidence, but one would probably want to start well before age 70 for this.

Internal Medicine

I was speaking to some colleagues and was surprised by the number who were not aware of less robust studies suggesting similar findings.

Neurology

The absolute benefit of aspirin in primary prevention of cardiovascular events has been small and unstable across studies. This is a study that puts caution to aspirin use in elderly patients who do not have cardiovascular disease.

Public Health

This study has already lead to a few discussions in clinic. Helpful in pruning out medication burden.

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