MEDIA
STATEMENT
3rd March 2010
AAAT trial, JAMA March 3rd 2010
The findings of the Aspirin for Asymptomatic Atherosclerosis Trial
(AAAT) were first announced in August 2009 at the European Society
of Cardiology Congress in Barcelona. The trial was intended to
find out whether low-dose aspirin would reduce the risk of cardiovascular
events such as heart attack in people who had atherosclerosis
but no symptoms. (The use of aspirin to reduce risk in people
with no symptoms is known as primary prevention.)
AAAT neither proved nor disproved the potential benefit of aspirin.
It did not show that aspirin reduced the risk of cardiovascular
events in people at low risk but nor could it exclude the possibility
of a beneficial effect. Considering AAAT in the context of three
meta-analyses of randomised trials of primary prevention with
aspirin,(1-3) the Aspirin Foundation does not expect the findings
to alter current clinical guidelines on prescribing aspirin for
people at moderate to high risk of cardiovascular events.(4-7)
There were several aspects of AAAT that made it unlikely to detect
an effect of aspirin:
• The selection criteria resulted in study population at
low risk of cardiovascular events, with mild peripheral vascular
disease at the start, a low frequency of coronary heart disease
during the trial (6% over 10 years) and a low 10-year cardiovascular
event rate (12.7%). These figures represent a risk level that
is below or borderline for recommending primary prevention with
aspirin according to current guidelines(4-7) and any effect of
aspirin would have been small in such a population.
• A large proportion of people randomised to treatment with
aspirin did not take it (amounting to 40% of patient-years of
treatment) and 15% did not take it for longer than 6 months; further,
15% of people assigned to take placebo took aspirin as well. This
would reduce differences between the aspirin and placebo arms
of the trial.
• The authors overestimated the effect of aspirin when they
designed the trial (they assumed it would reduce risk by 25% whereas
current evidence shows the true figure is 12% - 15%). As a result,
they did not include enough participants to give the trial the
statistical power needed to detect a difference between aspirin
and placebo. As a result, the trial’s findings are imprecise:
the possible effect of aspirin could range from a risk reduction
of 16% to an increased risk of 27%. The authors acknowledged that
“...aspirin might still have a net beneficial effect on
patients with a low ABI [ankle brachial index, an indicator of
peripheral vascular disease], elevated risk factors, and a greater
incentive to continue taking medication.”
• AAAT was originally intended to last for about 5 years
but the number of cardiovascular events was so low after this
time that it had to be extended for another 4.5 years to get enough
events for analysis. Then the trial was stopped 14 months early
when it became clear it would probably not detect an effect of
aspirin.
• There was no statistically significant difference in the
frequency of major bleeding between aspirin and placebo.
• AAAT adds only a little to the body of evidence on primary
prevention with aspirin - equivalent to about 3% of the total
patient population, or about 4% of the total treatment experience.
Ends
References
1. Antithrombotic Trialists’ (ATT) Collaboration. Aspirin
in the primary and secondary prevention of vascular disease: collaborative
meta-analysis of individual participant data from randomised clinical
trials. Lancet 2009;373:1849-60
2. Bartolucci A, Howard G. Meta-analysis of data from the six
primary prevention trials of cardiovascular events using aspirin.
Am J Cardiol 2006;98:746-50.
3. Eidelman RS et al. An update on aspirin in primary prevention
of cardiovascular disease. Arch Int Med 2003;163:2006-10
4. Pearson TA et al. AHA Guidelines for Primary Prevention of
Cardiovascular Disease and Stroke: 2002 Update. Circulation 2002;106:388-91
5. Mosca L et al. Evidence-Based Guidelines for Cardiovascular
Disease Prevention in Women: 2007 Update. Circulation published
online Feb. 19, 2007; DOI: 10.1161/CIRCULATIONAHA.107.181546;
J Am Coll Cardiol 2007;49:1230-50
6. Graham I et al. European guidelines on cardiovascular disease
prevention in clinical practice: full text. European J Cardiovasc
Prev Rehab 2007;14 (suppl 2):S1-S113.
7. US Preventive Services Task Force. Aspirin for the Prevention
of Cardiovascular Disease: US Preventive Services Task Force Recommendation
Statement. Ann Intern Med 2009;150:396-404
