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Aspirin for Asymptomatic Atherosclerosis - AAA — Presented at ESC 2009
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 will be associated with a reduction in the composite of coronary event, stroke or need for revascularization for primary prevention in patients with a low ABI.
Study Design
Study Design:
Patients Enrolled: 3350
Mean Follow Up: Mean 8.2 years
Mean Patient Age: 50 to 80 years
Female: 71
Patient Populations:
Men and women age 50 to 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; and an abnormally high or low packed cell volume.
Primary Endpoints:
Composite of initial fatal or nonfatal coronary event or stroke or revascularization
Secondary Endpoints:
(1) all initial vascular events defined as a composite of a primary endpoint event or angina, intermittent claudication or transient ischaemic attack; and (2) all cause mortality
Drug/Procedures Used:
Subjects (n=28,980) free of cardiovascular disease underwent ABI screening test. The ABI test is the ratio of systolic pressure at 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) or matching placebo (n = 1,675). The trial was powered to detect a 25% reduction in events with aspirin vs placebo.
Principal Findings:
The mean ABI at study entry was 0.86. Mean age was 62 years, and 29% were men. Participants were on treatment for 60% of person years of follow-up.
There was no difference in the primary endpoint of coronary event, stroke, or revascularization between the aspirin and placebo groups (10.8% vs 10.5%, respectively, hazard ratio [HR] 1.03, 95% 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 TIA (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 to 1.16, 10.5% vs 11.1%, p=NS). There was also no difference in stroke (0.4% vs 0.7%, p=NS) or non-fatal 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 to 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 coronary event, stroke or revascularization at a mean follow-up of 8.2 years compared with placebo, but 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 Trialist 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 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:
Presented by Dr. Gary Fowkes at the European Society of Cardiology Congress, Barcelona, Spain, August 2009.
Keywords: Intermittent Claudication, Stroke, Ankle Brachial Index, Scotland, Warfarin, Blood Pressure, Hemorrhage, Primary Prevention
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