The routine use of low-dose aspirin in healthy people, whether alone or as part of a ‘polypill’, to ward off the risk of cardiovascular (CV) or cerebrovascular disease is not justified when weighed against the greater risk of internal bleeding, a new study has concluded.

Results from the Aspirin for Asymptomatic Atherosclerosis (AAA) study, which were presented at the European Society of Cardiology’s (ESC) 2009 Congress in Barcelona, Spain, found no statistically significant difference in primary endpoint events – a composite of initial fatal or non-fatal coronary event or stroke, or revascularisation – between trial participants taking aspirin and those on placebo.

At the same time, the risk of a major bleeding event requiring hospital admission was nearly twice as high in the aspirin than the placebo group. The British Heart Foundation said the findings were in line with its current advice that people without symptomatic or diagnosed artery or heart disease “should not take aspirin, because the risks of bleeding may outweigh the benefits”.

The AAA study outcomes also chimed with the conclusions of a meta-analysis published earlier this year in The Lancet by the Antithrombotic Triallists’ Collaboration. This found that the modest benefits of low-dose aspirin in people without cardiovascular disease were offset by an increased risk of major gastrointestinal and extracranial bleeds.

The latest trial was presented at the ESC Congress by Professor Gerry Fowkes from the Wolfson Unit for Prevention of Peripheral Vascular Diseases in Edinburgh, Scotland. It was sponsored by the British Heart Foundation, the Chief Scientist Office of the Scottish Executive and branded aspirin manufacturer Bayer Healthcare.

The study was the first placebo-controlled randomised trial designed to evaluate the effects of aspirin in asymptomatic atherosclerosis as measured by a low ankle brachial index (ABI).

This is the ratio of systolic pressure at the ankle to that in the arm; in vascular practice it is used to confirm a diagnosis and assess the severity of peripheral atherosclerosis in the legs. Lower levels of the ABI are also associated with higher rates of concomitant coronary and cerebrovascular disease, and with the presence of cardiovascular risk factors.

The study recruited 28,980 men and women aged 50 to 70 years in central Scotland who were free of clinically evident cardiovascular disease. All of the participants underwent ABI screening and those with a low ratio (3,350 in total) were randomised to once-daily aspirin 100mg or placebo.

The participants were followed up for a mean of 8.2 years, with outcomes determined by annual contact, general practitioner records, linkage to discharges from Scottish hospitals or death notification. There were two secondary endpoints: all initial vascular events, defined as a composite of a primary endpoint event or angina, intermittent claudication or transient ischaemic attack; and all-cause mortality.

The results showed that 357 participants overall had a primary endpoint event, 181 in the aspirin group and 176 in the placebo group. A secondary-endpoint vascular event occurred in 578 participants, but once again there was no statistically significant difference between the aspirin (288 events) and the placebo (290) groups. All-cause mortality was 176 deaths and 186 deaths in the aspirin and placebo groups respectively.

An initial event of major bleeding that required hospital admission was observed in 34 (2%) of the subjects taking aspirin, compared with 20 (1.2%) of those on placebo.

“Although the AAA trial was not of screening per se, the results would suggest that using the ABI as a tool to screen individuals free of cardiovascular disease in the community is unlikely to be beneficial if aspirin is the intervention to be used in those found to be at higher risk,” Professor Fowkes commented.

“Other more potent antiplatelets might be considered, but only if increased effectiveness in avoiding ischaemic events is not matched by increased bleeding,” he added.