New anticoagulants show promise.

Two experimental pills could become alternatives to a class of drugs that's used widely to protect surgical patients against potentially fatal blood clots. Currently, many patients need repeated postoperative injections of anticoagulants such as heparin or related drugs.

The pills might also replace another anticoagulant, warfarin, which many people now take orally for months or years to counter clotting risks associated with cancer, certain heart conditions, or a history of blood clots, says Giancarlo Agnelli of the University of Perugia in Italy.

The new compounds inhibit a clot-promoting blood molecule called factor Xa. Most existing drugs have that effect and several others. Neither new compound has a permanent name yet. Bayer HealthCare of Leverkusen, Germany, calls the one it developed BAY 59-7939, and developer Eli Lilly and Co. of Indianapolis calls the other LY517717.

With Bayer funding, Alexander G.G. Turpie of McMaster University in Hamilton, Ontario, and his international collaborators tested that company's compound at five daily dosages in 1,102 patients undergoing hip- or knee-replacement surgery. The researchers gave a sixth group of patients injections of enoxaparin (Lovenox), a derivative of heparin.

All doses of the new Bayer compound prevented clots at least as well as did enoxaparin. In each study group, fewer than 5 percent of patients experienced serious clots called major deep-vein thromboses.

Four of the 236 enoxaparin-treated patients had dangerous bleeding after surgery, presumed to be caused by excessive anticoagulation. At doses of 5, 10, and 20 milligrams per day, the Bayer compound caused no more bleeding than enoxaparin did. However, doses of 40 and 60 mg/day of the new drug caused excess bleeding episodes, Turpie reported last week at a meeting in Atlanta of the American Society of Hematology.

Separately, researchers led by Agnelli and supported by Lilly compared that company's new compound with enoxaparin in 511 European and Australian volunteers who were undergoing hip or knee replacements.

At doses of 100, 125, and 150 mg/day, the new compound prevented major deep-vein thrombosis about as well as enoxaparin did. Lower doses of the test drug performed less well. The Lilly drug caused no more Needing than enoxaparin did, Agnelli reported in Atlanta.

The new compounds are "clearly superior," says hematologist Katherine A. High of the University of Pennsylvania in Philadelphia. They don't require injections as enoxaparin and related drugs do, and they appear to be as effective and as safe at a range of doses.

Balancing clot prevention and bleeding risk is a particularly delicate act with warfarin. Agnelli estimates that as many as 4 million U.S. residents use the inexpensive pills, which are sold as Coumadin, for example. Patients must see their doctors at least once a month to make sure that their dosages are neither too high nor too low.

"Our dream is to replace warfarin," says Agnelli.