Peters first presented the data on this CURE substudy at the 2002 American Heart Association meeting. The patients in CURE were divided into three aspirin dose groups: 100 mg or less (n=5320), 101 mg to 199 mg (n=3109), and 200 mg or more (n=4110).

The message to clinicians is not to increase the dose of aspirin in order to compensate for not having clopidogrel.

Among the clopidogrel-treated patients, the amount of aspirin taken daily did not significantly affect the rate at which they suffered a cardiovascular death, MI, or stroke. Nor was there a significant difference in these outcomes among the three aspirin doses in the aspirin-only group.

But higher aspirin doses were associated with a higher risk of major bleeding, and the excess rate of major bleeding seen in those taking clopidogrel now seems to have been largely due to the aspirin dose used.

"The bleeding rate was in fact slightly lower for low-dose aspirin plus clopidogrel than for high-dose aspirin alone," Peters says. He says one important message from this is that in situations where clopidogrel is not available, "the message to clinicians is not to increase the dose of aspirin to compensate for not having clopidogrel,"

Within each participating institution, aspirin dose did not vary significantly, but across geographic regions the range was much larger, Peters noted. The highest dose was most common in Canada and the US, while researchers in Latin America were the second most likely to use a high-dose aspirin regimen. The medium doses were used in Australia and New Zealand, and the lowest doses were used in Eastern and Western Europe. The median dose of aspirin used in the study was 150 mg.

Peters notes that other factors also increase the risk of bleeding, such as combinations of antithrombotics and interventions such as CABG. "In the past 10 years, adding in new antithrombotic therapies on top of old ones has made the issue of safety even more critical," he commented to heartwire. Although it is difficult to be precise, common sense dictates that patients undergoing interventions and taking lots of antithrombotic medications should be on lower doses of aspirin, he says.

In the past 10 years, adding in new antithrombotic therapies on top of old ones has made the issue of safety even more critical.

Peters says there is a minimum necessary dose of aspirin, which he believes is 75 mg a day, and that 75 mg to 100 mg is the optimum dose for long-term secondary prevention. CURE was an acute-plus-one-year-of-secondary-prevention study, and other experts have stressed that there are certain situations whereby much higher doses of aspirin should be used, such as for acute events and for the first few weeks after stent placement.

On the issue of whether there should be a megatrial of low-dose vs high-dose aspirin, as has been suggested by others, Peters told heartwire that the cost of such a trial might preclude it from ever taking place, "and for practical purposes, we probably know enough." However, "scientifically, there is still a need for such a megatrial as all the results we have so far are retrospective and observational."