Oral anticoagulation: improving the risk-benefit ratio

For four decades, warfarin has been used extensively to treat thromboembolic disorders. Major advances in monitoring have been achieved through recognition of thromboplastin variability and implementation of the international normalized ratio (INR). Recommended INR ranges have shifted to lower intensity, and new clinical information has led to the potential for increased use of warfarin to prevent venous thromboembolism, to treat patients with prosthetic heart valves, to prevent stroke in patients with atrial fibrillation, and to prevent death and recurrent events after myocardial infarction. Optimal management of the patient who requires a drug that has a narrow therapeutic index, such as warfarin, remains challenging. Strategies to enhance patient outcomes with these drugs attempt to improve the risk-benefit ratio of such therapies, which requires optimizing the agent's effectiveness, improving its safety profile, or both.