A UK study presented at a conference last weekend found no evidence to support the idea that a daily dose of aspirin protects people who do not have artery or heart disease from developing it in the future any better than a placebo, and experts suggest given the higher risk of internal bleeding from taking aspirin routinely, for healthy people such a precaution may do more harm than good.

The study reported results from the Aspirin for Asymptomatic Atherosclerosis (AAA) study, whose joint first author Professor Gerry Fowkes from the Wolfson Unit for Prevention of Peripheral Vascular Diseases in Edinburgh, presented the findings at the European Society of Cardiology (ESC) Congress 2009 in Barcelona, Spain on Sunday.

Fowkes said the study was the first placebo-controlled randomised trial to test the protective effect of aspirin in people who did not show signs of atherosclerosis as measured by a low ankle brachial index (ABI) at the start of the study, and that the results found:

“No statistically significant difference in primary endpoint events between those subjects allocated to aspirin or placebo.”

ABI compares the blood pressure in the lower legs to the blood pressure in the arms and is a measure of whether peripheral artery disease might be present.

Studies have already shown that antiplatelet drugs like aspirin are effective in secondary prevention, where people who already have arterial disease, or have suffered a stroke or heart attack, use them to prevent a further event.

But as Fowkes explained, there was little evidence about how effective routine use of these drugs might be in primary prevention, that is protecting people who have not yet developed arterial or heart disease from getting it in the future, so that any benefits in this direction might be weighed up against the already known risk of bleeding.

The trial recruited 28,980 men and women who were living in central Scotlan and were aged from 50 to 75 years. Al the participants were free of clinically evident cardiovascular disease and went through ABI screening.

3,350 participants with low ABI (under or equal to 0.95) were then randomized to taking a once daily 100 mg dose of aspirin or equivalent placebo.

The researchers then followed them for an average of 8.2 years, using a mix of annual contact, looking at GP records, discharge reports from Scottish hospitals, and death notifications.

They looked for two kinds of information in the follow up, which they grouped according to whether they were primary or secondary endpoints of interest to the study.

The primary endpoints they looked for in the follow up records were: initial fatal or non-fatal coronary event or stroke, or revascularisation. They used this as a composite figure in the analysis.

They looked for two secondary endpoints: (1) all initial vascular events defined as a composite of a primary endpoint event or angina, intermittent claudication or transient ischaemic attack, or (2) death from all causes.

The results showed that:

  • 357 participants had a primary endpoint event (reflecting a rate of 13.5 primary events per 1,000 person years).

  • 181 of these were in the aspirin group and 176 were in the placebo group, with no statistically significant difference between them.

  • 578 participants had a secondary endpoint vascular event, 288 in the aspirin and 290 in the placebo group, also with no statistically significant difference between them.

  • Death from all causes was also similar in both groups (176 people died in the aspirin group and 186 in the placebo group).

  • 34 (2 per cent) of the aspirin group participants had an initial event of major bleeding that required hospital admission, compared to 20 (1.2 per cent) in the placebo group.

Fowkes said:

“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.”

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

The study was part funded by the British Heart Foundation, whose Medical Director, Professor Peter Weissberg said:

“We know that patients with symptoms of artery disease, such as angina, heart attack or stroke, can reduce their risk of further problems by taking a small dose of aspirin each day.”

“The findings of this study agree with our current advice that people who do not have symptomatic or diagnosed artery or heart disease should not take aspirin, because the risks of bleeding may outweigh the benefits,” he added.

However, other experts might suggest that the study’s findings are too bound up with the issue of using ABI as the screening tool, and the question of whether these results would be different with another screening tool remains unanswered.

As Fowkes himself pointed out:

“It is possible that in the general population, aspirin could produce a smaller reduction in vascular events than this trial was designed to detect, but it is questionable whether such an effect, together with aspirin related morbidity, would justify the additional resources and health care requirements of an ABI [ankle brachial index] screening programme.”

Speaking at another session the day before, Gilles Montalescot from the University Hospital of Pitié-Salpètrière in Paris, emphasized the difference between using aspirin and other NSAIDs (non-steroidal anti-inflammatory drugs) in primary and secondary prevention of strokes.

“If the net cerebrovascular benefit is in favour of aspirin in secondary prevention, it is a different story in primary prevention where the protection against ischemic stroke is offset by the risk of intracranial bleeding,” said Montalescot.

Speaking at the same session, Carlo Patrono of the Catholic University School of Medicine in Rome, Italy, who worked on the AAA trial with Fowkes, said aspirin should be trialled further, as it may offer potential benefits in treating other diseases:

“Additional benefits of long-term aspirin therapy in preventing other serious outcomes, such as colorectal cancer, are not yet established by randomised clinical trials.”

“However, the demonstrated efficacy of low-dose aspirin in reducing the risk of recurrence of sporadic colorectal adenomas is promising in this respect,” added Patrono.

“Randomised controlled trial of low dose aspirin in the prevention of cardiovascular events and death in subjects with asymptomatic atherosclerosis.”
Gerry Fowkes and Carlo Patrono.
Presented at the European Society of Cardiology (ESC) Congress 2009, Barcelona.
Hot Line 1, Session 175-176, on 30 August 2009.

Other sources: BHF.

Written by: Catharine Paddock, PhD