The clinical implications of new oral anticoagulants: will the potential advantages be achieved?

With the advent of new oral anticoagulants a thorough assessment and evaluation of benefits weighed against potential risks must be conducted. In a practical sense, what will these new agents really offer to the healthcare system, to practitioners, and to patients? Oral anticoagulation with the vitamin K antagonist (VKA), warfarin, continues to increase worldwide due to its efficacy in preventing stroke in patients with atrial fibrillation (AF) or recurrent thromboembolism in patients with thromboembolic disease (1). Despite warfarin’s efficacy, its management remains problematic due to its complex pharmacokinetic and pharmacodynamic properties and narrow therapeutic range. Warfarin therapy requires vigilant coagulation monitoring, clinical surveillance, and continuous patient education ( Table 1). Due to these dosing complexities, warfarin is associated with a high rate of adverse events that creates barriers to more widespread use (2, 3). The development of new anticoagulants has been pursued with the aim of finding effective, but safer and more convenient therapies. Many of the new agents attempt to meet the goals of an ideal anticoagulant ( Table 2) by targeting a specific step or factor in the coagulation pathway. Among agents that are most advanced in clinical research, and rapidly becoming approved for specific indications, are the direct thrombin (factor IIa [FIIa]) inhibitors and the direct factor Xa (FXa) inhibitors (4–7). Ximelagatran, an oral, direct thrombin inhibitor, was the first to undergo extensive testing showing that it was at least as effective and safe as warfarin for stroke prevention in AF (8, 9) and for the secondary prevention of venous thromboembolism (VTE) in patients with established VTE (10). It also showed effectiveness in patients with acute coronary syndromes (11). Because of hepatic toxicity, however, the drug was removed from the market and is no longer in development.