Low-dose aspirin inhibits platelet aggregation without increasing the risk for a significant bleeding event, according to findings published in the September 23rd rapid access issue of Circulation. The new findings on effects of various dosages of aspirin came from a large international trial called the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study.

The major aim of the trial was to compare the combination of clopidogrel and aspirin with aspirin alone as treatment for unstable angina. The study involved 12,562 patients who were prescribed aspirin and randomized to clopidogrel or placebo. Researchers reported last year that there were significantly fewer severe cardiovascular events in the combination arm than in the aspirin arm (9.3 percent and 11.4 percent, respectively).

In addition, the trial, which involved 12,562 people, was designed to evaluate safety and efficacy of various aspirin doses, alone or in combination with clopidogrel. The study protocol recommended a daily aspirin dose between 75 mg and 325 mg, although individual dosing was left to the prescribing physician. In the current analysis, aspirin use was divided into three groups; less than or equal to 100 mg, 101 through 199 mg, and 200 mg or greater. Among the study participants, 5,320 received the low dose, 3,109 took the medium dose, and 4,110 got a high dose.

Lead author Ron J.G. Peters, M.D., lead author of the study, commented “Experimentally, a single 100-milligram dose of aspirin is sufficient in healthy individuals to inhibit platelet aggregation.”

The analysis in the current article has three major points. First, the benefit of clopidogrel did not vary significantly with dose of aspirin. Higher doses of aspirin were associated with increased risk for major bleeding events, and this increase in risk was independent of whether aspirin was used alone or in combination with clopidogrel. In addition, higher doses of aspirin were not associated with a lower rate of cardiovascular events. Thus, the authors suggest that the optimal aspirin dose for reducing acute coronary syndromes may be between 75 and 100 mg daily.

Among the clopidogrel-treated patients, the amount of aspirin taken daily did not significantly affect the rate for cardiovascular death, myocardial infarction, or stroke. There was no significant difference in outcomes among the three aspirin doses in the aspirin-only group.

However, “major bleeding complications increased significantly with increasing aspirin dose, both in the placebo and the clopidogrel group,” Peters said. “The bleeding rate was in fact slightly lower for low-dose aspirin plus clopidogrel than for high-dose aspirin alone.”

In the placebo group, the bleeding risk was 1.9 percent with low-dose aspirin, 2.8 percent with medium-dose aspirin, and 3.7 with high-dose aspirin. Bleeding risks for the clopidogrel patients were 3.0 percent on low-dose aspirin, 3.4 percent on medium-dose aspirin, and 4.9 percent on high-dose aspirin.

“This type of evidence will certainly be very important in the development of our revised guidelines for aspirin use,” said Sidney C. Smith, M.D., former chief science officer and a national spokesperson for the American Heart Association.