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Powerful clot blocker may revolutionize treatment of severe chest pain

March 18, 1997

ANAHEIM, Calif. (AP) _ A powerful new clot-preventing medicine appears to cut the risk of heart attack and death almost in half in people hospitalized with severe chest pain, a medical emergency that afflicts more than 1 million Americans annually.

The drug is one of a new class of medicines that are likely to revolutionize the treatment of unstable angina, an ominous attack of chest pain that is the leading reason for admitting people to coronary care units.

The medicine is a sort of super aspirin that works by stopping the formation of blood clots. These clots can trigger heart attacks by choking off the supply of blood to the heart muscle.

Currently, aspirin and a blood thinner called heparin are the mainstays of treatment for unstable angina. The new medicine proved to be powerfully effective when used in addition to these.

Doctors say the new therapy may turn out to be even more important than clot-dissolving drugs, an entirely different group of medicines that have transformed the treatment of heart attacks over the past decade.

``These are landmark studies that represent a scientific breakthrough,″ said Dr. Harvey D. White of Green Lane Hospital in Auckland, New Zealand.

White said the drug will save the lives of 13 of every 1,000 unstable angina patients treated. By comparison, TPA, the leading clot-dissolver, saves 10 of every 1,000 heart attack patients treated.

White directed one of two large studies on the drug, called Aggrastat, that were released Monday at a meeting of the American College of Cardiology.

Dr. Rick Sax, who developed the drug at Merck & Co., estimated that if all the 1.2 million unstable angina patients hospitalized in the United States each year received Aggrastat, it would prevent between 5,000 and 10,000 deaths and 30,000 to 40,000 heart attacks.

Aggrastat is still considered experimental. Merck plans to ask the Food and Drug Administration later this year for permission to put it on the market.

The medicine is available only as an injection for use in the hospital, but at least 19 new versions are being developed in pill form for long-term use in people with bad hearts.

A similar drug, Centocor’s ReoPro, is already available but has been tested only for use during angioplasty, the technique used to reopen clogged blood vessels.

Aggrastat’s success is likely to trigger an avalanche of similar medicines to capture a huge potential market.

The approach ``really opens up the treatment of unstable angina,″ said Dr. Eugene Braunwald of Brigham and Women’s Hospital in Boston, who was not involved in the studies. ``It’s a real advance. I’m encouraged.″

Typically, unstable angina occurs when a fatty buildup on an artery wall breaks open during some form of stress. Blood cells called platelets congregate in this wound and clump together. In the narrow confines of an artery, this clot can be disastrous, for it may block blood flow entirely.

The platelets are hooked together by a protein called fibrinogen, which latches onto spots on the cells called glycoprotein IIb-IIIa receptors. Aggrastat _ or tirofiban _ is one of a class of medicines called glycoprotein IIb-IIIa blockers. As the name implies, the medicine keeps fibrinogen from linking up platelets to form clots.

Actually, 90 different biochemical triggers can start the cascade of steps that lead to clots. Aspirin blocks one of these steps. Aggrastat blocks all of them.

In one of the new studies, 1,615 patients with unstable angina were randomly assigned to get aspirin plus heparin or aspirin plus Aggrastat. One month later, 3.6 percent of the heparin patients had died, compared with 2.3 percent of the Aggrastat patients _ a 39 percent reduction in death.

The other study was conducted on 1,570 even more severely afflicted patients, including some with mild heart attacks called non-Q-wave infarctions. In this study, all patients got both heparin and aspirin, and half took Aggrastat as well.

Aggrastat reduced the risk of heart attacks in the following week by approximately 44 percent: Seven percent of those getting heparin and aspirin alone got heart attacks, compared with 3.9 percent of those who got Aggrastat in addition. Heart attacks and deaths combined dropped about 41 percent.

``This is a powerful approach. We have shown that it is clearly effective,″ said Dr. Pierre Theroux of the Montreal Heart Institute, one of the researchers.

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