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. 379(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 70 years or older, but was associated with higher rates of major hemorrhage and 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

  • Median age 74 years, 56% Female
  • BMI: 28.1
  • Hemoglobin: 14.2
  • Fasting glucose: 98.9
  • HDL 61.5, total cholesterol 202.7
  • Creatinine 0.9, eGFR 73
  • SBP 139 ± 17 mmHg, DBP 77 ± 10 mmHg

values are means

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 events per 1,000 person-years in the aspirin group vs 21.2 for each 1,000 person-years in the placebo group (HR = 1.01; 95% CI, 0.92-1.11)

Secondary Outcomes

All-cause mortality
12.7 events per 1,000 person-years in the aspirin group vs 11.1 events per 1000 person-years in the placebo group (HR, 1.14; 95% confidence interval [CI], 1.01 to 1.29)
Cancer-related death
6.7 events per 1,000 person-years in the aspirin group vs 5.1 events per 1000 person-years in the placebo group (HR, 1.31; 95% CI, 1.10 to 1.56)

Subgroup Analysis

Adverse Events

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

Criticisms

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

Funding

Further Reading