Aspirin for Asymptomatic Atherosclerosis - AAA

Mar 02, 2010
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Author/Summarized by Author:
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Summary Supplemental Reviewer:
Anthony A. Bavry, MD, MPH, FACC
Trial Sponsor:
British Heart Foundation, Chief Scientist Office of the Scottish Executive, and Bayer Healthcare 
Date Presented:
01/01/2009
Date Published:
01/01/2010
Date Updated:
03/02/2010
Original Posted Date:
03/02/2010
References

Description:

The goal of the trial was to evaluate treatment with aspirin compared with placebo for primary prevention among patients with a low ankle brachial index (ABI).

Hypothesis:

Use of low-dose aspirin would be associated with a reduction in the composite outcome of a fatal or nonfatal coronary event, stroke, or revascularization for primary prevention in patients with a low ABI.

Study Design

  • Randomized

Patients Screened: 28,980
Patients Enrolled: 3,350
Mean Follow Up: 8.2 years
Mean Patient Age: 62 years
Female: 72

Patient Populations:

  • Men and women ages 50-80 years and free of cardiovascular disease were recruited from general practice registers in Lanarkshire, Glasgow, and Edinburgh in Scotland and had an ABI screening test.
  • Those with a low ABI (≤0.95) who were not already taking routine aspirin or warfarin and volunteered were included.

Exclusions:

  • Severe indigestion
  • History of MI, stroke, angina, or peripheral arterial disease
  • Chronic liver or kidney disease
  • Chemotherapy
  • Contraindications to treatment with aspirin
  • An abnormally high or low packed cell volume

Primary Endpoints:

  • Composite of initial fatal or nonfatal coronary event or stroke or revascularization

Secondary Endpoints:

  • All initial vascular events defined as a composite of a primary endpoint event or angina, intermittent claudication, or transient ischemic attack
  • All-cause mortality

Drug/Procedures Used:

Subjects (n = 28,980) free of cardiovascular disease underwent ABI screening (ratio of systolic pressure in the ankle to that in the arm). Patients with low ABI (≤0.95) were randomized in a double-blind manner to 100 mg enteric coated aspirin (n = 1,675) versus matching placebo (n = 1,675). The trial was powered to detect a 25% reduction in events with aspirin versus placebo.

Concomitant Medications:

At baseline, in the aspirin group, diuretics were used in 15.5%, beta-blockers in 10.0%, nitrates/calcium channel blockers in 6.6%, angiotensin-converting inhibitors/angiotensin-receptor blockers in 6.3%, and lipid-lowering agents in 4.1%.

Principal Findings:

The mean ABI at study entry was 0.86. Mean age was 62 years, and 72% were women.

There was no difference in the primary endpoint of fatal or nonfatal coronary event, stroke, or revascularization between the aspirin and placebo groups (10.8% vs. 10.5%, respectively, hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.84-1.27, p = NS). Likewise, there was no difference between the aspirin and placebo groups in the secondary composite endpoint, which included the primary endpoint plus angina, intermittent claudication, and transient ischemic attack (HR 1.00, 95% CI 0.85-1.17, p = NS) or in the secondary endpoint of all-cause mortality (HR 0.95, 95% CI 0.77-1.16, p = NS). There was also no difference in nonfatal stroke (2.2% vs. 2.3%, p = NS) or nonfatal myocardial infarction (MI) (3.7% vs. 4.1%, p = NS). Major bleeding requiring hospital admission occurred in 2.0% of the aspirin group and 1.2% of the placebo group (HR 1.71, 95% CI 0.99-2.97).

Interpretation:

Among patients with a low ABI but no known cardiovascular disease, treatment with enteric coated aspirin was not associated with a difference in the composite endpoint of a fatal or nonfatal coronary event, stroke, or revascularization at a mean follow-up of 8.2 years compared with placebo. Aspirin therapy was associated with an increase in major bleeding.

The efficacy of aspirin for secondary prevention following a cardiovascular event has been well established in several large-scale trials, as well as in a patient-level meta-analysis by the Antithrombotic Trialists' Collaboration. However, the effect of aspirin for primary prevention has not been studied as extensively and has shown mixed results in the trials that are available. Low-dose aspirin decreased the risk of first MI by 44% compared with placebo in the Physician's Health Study. In the Women’s Health Study, there was no significant difference in major cardiovascular events, but stroke was lower in women randomized to aspirin compared with placebo.

Healthy subjects with a low ABI have previously been shown to be at high risk for future vascular events independent of other clinical cardiovascular risk factors. Despite the higher risk for vascular events, aspirin had no impact on vascular events in the present study, but did increase major bleeding. The compliance was relatively low in the study (60%), which could have contributed to the null findings. In addition, a relatively large treatment effect (25% RRR) was needed to detect a difference and it is possible that the study was underpowered to detect a smaller difference.

References:

Fowkes FG, Price JF, Stewart MC, et al. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA 2010;303:841-8.

Presented by Dr. Gary Fowkes at the European Society of Cardiology Congress, Barcelona, Spain, August 2009.

Keywords: Intermittent Claudication, Myocardial Infarction, Stroke, Ischemic Attack, Transient, Platelet Aggregation Inhibitors, Ankle Brachial Index, Scotland, Warfarin, Blood Pressure, Hemorrhage, Primary Prevention


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