New Drug Holds Promise to Block Clots in People with Artery Disease

FOR RELEASE: 4 p.m. EDT, MondayApril 29, 2002

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American Heart Association journal news briefNew drug holds promise to block clots in people with artery disease

DALLAS, April 30 -- The first study of a new drug designed to block blood clot formation showed no major adverse effects in people with stable coronary artery disease, according to a report in today's rapid access issue of Circulation: Journal of the American Heart Association.

The compound, DX-9065a, inhibits the action of factor Xa, one of the thirteen known factors involved in forming blood clots in coronary arteries. Factor Xa activates an enzyme called thrombin, which promotes the conversion of fibrinogen into fibrin, a major component of blood clots.

"This is the first clinical experience with a direct, selective, reversible factor Xa inhibitor in patients with coronary artery disease," says cardiology researcher Robert A. Harrington, M.D., of the Duke Clinical Research Institute, in Durham, N.C. "Our findings should lay the groundwork for further investigation of this and other agents that inhibit factor Xa in people with atherothrombosis, ischemic heart disease, and those undergoing coronary bypass surgery."

Anticoagulants, or blood-thinning drugs, work by inhibiting the ability of the blood to clot. Blood clots lodged in the coronary arteries block blood flow to the heart and cause most heart attacks. Anticoagulant therapy is commonly prescribed for people with heart disease to prevent further clot formation. The biggest drawback for anticoagulant drugs has been the potential for bleeding complications.

The randomized, double blind, placebo-controlled study, dubbed XaNADU, involved 73 patients with stable coronary artery disease at 10 medical centers. Their median age was 63 years, and 29 percent were women. Most had suffered a prior heart attack or had undergone angioplasty or coronary artery bypass surgery. During the study, 15 patients received a placebo, while 58 people received one of four different doses of DX-9065a, administered continuously over 72 hours.

Incidence of bleeding was minor and usually around the infusion site, and there was no statistically significant difference in bleeding complications between the five groups. Also, there were no adverse changes in kidney or liver function, and the hemoglobin and platelet counts remained stable across all groups.

"Even if this proves to be a modest advance, modest steps forward in treating a disease that affects millions of people every year is pretty good," says Harrington. Further trials are needed to study whether the new agent can reduce clotting, while minimizing bleeding, in a larger group of patients, he adds.

DX-9065a was developed by Daiichi Pharmaceutical Co., Ltd., a Tokyo-based firm with its U.S. headquarters in Fort Lee, N.J.

Co-authors are Christopher K. Dyke, M.D.; Richard C. Becker, M.D.; Neal S. Kleiman, M.D.; Judith S. Hochman, M.D.; Edwin G. Bovill, M.D.; Michael Lincoff, M.D.; Gary Gerstenblith, M.D.; Vladimir Dzavik, M.D.; Laura H. Gardner, BSPH; Vic Hasselblad, Ph.D.; Linda A. Zillman, R.N.; Yoshimasa Shimoto, Ph.D.; Thomas L. Robertson, M.D.; Satoshi Kunitada, Ph.D.; and Paul W. Armstrong, M.D.

###NR02 -- 1069 (Circ/Harrington)