A new oral anticoagulant: the 50-year challenge

It is rare for any drug introduced more than 50 years ago to remain unsurpassed today; yet the oral prevention and treatment of thrombosis are still achieved by the use of the vitamin K antagonists (coumarins), such as warfarin, which were introduced in the 1940s and 1950s. For these anticoagulants, careful monitoring of the effect is needed to avoid bleeding or loss of efficacy. On the basis of the need for improved oral anticoagulants, a goal was set in 1985 to develop a new oral anticoagulant that could replace the vitamin K antagonists. After providing some medical and historical context, this article discusses the challenges facing the multidisciplinary team of scientists who were involved in the project leading to the discovery of the anticoagulant ximelagatran (Exanta; AstraZeneca), the first oral direct thrombin inhibitor.