ASPREE

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McNeil JJ, et al. "Effect of aspirin on disability-free survival in the healthy elderly". The New England Journal of Medicine. 2018. e-pub 2018-09-16:1-10.
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Clinical Question

Does daily low-dose aspirin reduce disability-free survival in healthy seniors?

Bottom Line

Compared to placebo, low-dose aspirin was not associated with a reduction in disability-free survival in healthy adults at or above 70 years of age but was associated with higher rates of major hemorrhage as well as all-cause mortality.

Major Points

While daily Aspirin use has clear and well-described benefits for secondary prevention among patients with cardiovascular and cerebrovascular disease, its clinical utility in healthy, older adults had not previously been determined in a large trial.

The Effect of Aspirin on Disability-free Survival in the Healthy Elderly (ASPREE; 2018) trial enrolled 19,114 healthy elderly patients (≥70 years old, ≥ 65 years old in Hispanic or Black patients) without a history of cardiovascular disease, cerebrovascular disease, dementia, or any other chronic condition that would likely limit survival to less than 5 years. Patients were randomized to either Aspirin 100mg daily or placebo and followed prospectively for all-cause death, dementia, or physical disability. With a median follow-up of 4.7 years, rates of disability-free survival were similar between Aspirin and placebo groups (21.5 and 21.2 events per 1000 person-years, respectively). Additionally, the Aspirin group was linked with higher clinically-significant rates of major hemorrhage as well as all-cause mortality compared to the placebo group.

Design

  • Multicenter, randomized, double-blind, placebo-controlled
  • N=19,114
    • Aspirin (n=9,525)
    • Placebo (n=9,589)
  • Setting: 34 sites in the United States and 16 sites in Australia
  • Enrollment: 2010-2014
  • Median follow-up: 4.7 years
  • Analysis: Intention-to-treat
  • Primary outcome: Disability-free survival

Population

Inclusion Criteria

  • Men and women age 70 years and older
  • Ability to provide informed consent

Exclusion Criteria

  • History of diagnosed cardiovascular event (myocardial infarction, heart failure, peripheral artery disease, angina pectoris, stroke, transient ischemic attack, >50% carotid artery stenosis, prior carotid endarterectomy, prior coronary artery angioplasty or stenting, prior coronary artery bypass graft, or known abdominal aortic aneurysm)
  • Diagnosis of atrial fibrillation
  • Serious intercurrent illness expected to cause death within 5 years
  • A condition with high risk of bleeding (any bleeding diathesis, GI malignancy, recent PUD, liver disease, uremia, cerebral or aortic aneurysm, etc)
  • Anemia
  • Allergy to aspirin or other absolute contraindication
  • Systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 105 mmHg
  • Preexisting dementia or modified mini mental state exam score ≤ 77
  • Preexisting difficulty performing one of the 6 Katz activities of daily living
  • Pill-taking compliance < 80% during the initial run-in phase

Baseline Characteristics

Interventions

Patients were randomized into two groups to receive either: 1) enteric-coated Aspirin 100mg daily 2) matching placebo

Outcomes

Presented as aspirin vs. placebo. P-Y is person-years.

Primary Outcome

Disability-free survival
Defined as all-cause mortality, dementia, or persistent physical disability.
21.5 vs. 21.2/1000 P-Y (HR 1.01; 95% CI 0.92-1.11; P=0.79)

Secondary Outcomes

All-cause mortality
From another paper published simultaneously.
5.9% vs. 5.2% (HR 1.14; 95% CI 1.01-1.29)
Cancer: 3.1% vs. 2.3% (HR 1.31; 95% CI 1.10-1.56)
CVD including stroke: 1.0% vs. 1.2% (HR 0.82; 95% CI 0.62-1.08)
Major hemorrhage including hemorrhagic stroke: 0.3% vs. 0.3% (HR 1.13; 95% CI 0.66-1.94)
Other: 1.5% vs. 1.3% (HR 1.16; 95% CI 0.91-1.48)
CVD events
From another paper published simultaneously.
10.7 vs. 11.3/1000 P-Y (HR 0.95; 95% CI 0.83-1.08)
Major adverse CV event
Defined as...'
CVD mortality:
HF hospitalization:
Fatal or nonfatal MI:
Fatal or nonfatal ischemic stroke:

Subgroup Analysis

Adverse Events

 % vs. % (## HR; 95% CI ##-##; P=##; NNH=##)

Criticisms

- possible lack of generalizability (91.3% of participants were white)

Funding

Further Reading