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DURHAM, N.C. In the first head-to-head comparison against one of the newest oral heart drugs, aspirin has been shown to be just as effective in preventing heart attacks and had fewer bleeding side effects.

In an international study of 9,233 heart patients, researchers found that aspirin, an inexpensive mainstay of heart attack prevention, withstood the challenge from sibrafiban, a member of a class of drugs known as glycoprotein IIb/IIIa receptor antagonists.

This is the third member of this class of drugs - sometimes referred to as "super aspirin" - that has been shown to be less effective when taken as a pill than regular aspirin. Intravenous forms of two other members of this class of drugs for use in the hospital have been approved by the FDA. They are routinely used by cardiologists.

"Given the substantial benefit of aspirin alone and its low cost and lower bleeding risks, none of the completed studies provides evidence that would justify use of an oral glycoprotein IIb/IIIa receptor antagonist," said Duke cardiologist Dr. Kristin Newby, lead author of a study published Friday in the journal The Lancet.

The study, known as SYMPHONY (sibrafiban versus aspirin to yield maximum protection from ischemic heart events post-acute coronary syndromes), involved 670 hospitals in 33 countries, was coordinated by the Duke Clinical Research Institute and was funded by Hoffman-La Roche, of Basil, Switzerland.

"These new oral agents have neither met expectations nor matched the consistent track record of efficacy shown with the intravenous administration of such agents," Newby said. "More investigation of platelet-receptor biology and further detailed analysis of continuing clinical trials of agents with different properties are needed."

While researchers still are not certain about the exact mechanisms behind aspirin's effect, it appears that its main benefit is keeping platelets circulating in the blood from clumping together and forming clots. Aspirin also has the ability to reduce inflammation, which further research may show to be just as important, Newby said. Sibrafiban works by blocking a specific receptor on the surface of platelets, preventing them from clumping together.

"We know that taking aspirin reduces the risk of heart attack by about 25 percent, which is good, but we test new medications to see if we can improve on that rate even more," Newby said. "The results of this trial tell us that there is obviously more that we need to learn about the role of platelets and antiplatelet therapy and their interactions with other mediators of coronary artery disease."

In the randomized, double-blind trial, heart patients either took aspirin, or a low or high dose of sibrafiban within seven days of a cardiac event. After 90 days, researchers measured the number of adverse events, such as death, another heart attack or side effects.

While all three groups had analmost identical number of adverse effects after 90 days (9.8 percent for aspirin, 10.1 percent for both doses of sibrafiban), major bleeding events were higher in the sibrafiban groups - 5.2 percent for low-dose and 5.7 percent for high-dose, compared to 3.9 percent for aspirin.

Although a majority of the bleeding episodes were "nuisance" events from the nose or gums, some of the events were severe enough to warrant blood transfusions.

Cardiologists would like to develop a pill form of glycoprotein IIb/IIIa receptor antagonists so their patients can take the drug at home to prevent heart attacks, just as many do now with aspirin. The IV forms of the drugs are inconvenient and impractical because they must be administered in a hospital setting.

Two previous trials, OPUS (Orbofiban in Patients with Unstable coronary Syndromes) and EXCITE (Evaluation of Xemilofiban in Controlling Thrombotic Events) studied aspirin in combination with different glycoprotein IIb/IIIa receptor antagonists. Although the designs of the two trials were different, like SYMPHONY, they found that the new agent was no more effective than aspirin.

"All three of these glycoprotein IIb/IIIa receptor antagonists work in a similar fashion, but there are subtle differences in the way they interact with platelet receptors and their pharmacologic characteristics in patients," Newby said. "It appears that we may need to better understand the complex interactions of the inhibitors before we can develop a drug significantly more effective than aspirin."