More than 70 years ago, a farmer approached scientists at the University of Wisconsin asking them to solve a mystery involving spoiled sweet clover, a dead heifer and bovine blood that wouldn't clot. What the researchers found -- that the rotting clover triggered a chemical reaction that caused internal bleeding -- eventually led to the creation of warfarin, an anticoagulant that has played a key role in preventing debilitating and fatal blood clots. Over the years, warfarin has been the target of companies that believed they could make a better, more convenient drug, and capitalize on a market where many patients must take anticoagulants for the remainder of their lives. Warfarin pills are sold generically and by Bristol-Myers Squibb ( BMY) under the brand name Coumadin. "Anything that could supplant Coumadin would be widely used," says Albert Rauch, an analyst with A.G. Edwards. "They could expand the market." Several companies hope to do just that. Currently, Eli Lilly ( LLY) Germany's Boehringer Ingleheim and Bayer ( BAY), and the Anglo-Swedish firm AstraZeneca ( AZN) have drugs in clinical testing. However, many challengers have failed, and warfarin has proven durable. The key issue is "to design something that can be taken by mouth and efficiently absorbed into the blood stream as a therapeutically effective agent," says Dr. Thomas Ortel, director of the hemostasis and thrombosis center at the Duke University School of Medicine. "New drugs have to be looked at carefully because patients may be on them for a long time, and long-term side effects may not be identified with relatively short clinical trials." The most notable recent failure was Exanta from AstraZeneca. In clinical trials, the Exanta pill was as effective as warfarin in preventing clots and strokes. Exanta was easier to administer, and it interacted with far fewer drugs.