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Currently, the only oral anticoagulants available for use in chronic conditions are vitamin K antagonists (VKAs), of which the most frequently used is warfarin. The VKAs have been shown to be effective for primary and secondary prevention of venous thromboembolism, for prevention of arterial embolism as well as acute myocardial infarction, and stroke. However, the clinical utility of VKAs is limited by variability in patient response, numerous drug and food interactions, and a narrow therapeutic window.
The package insert for warfarin, lists 81 drug classes, 174 specific drugs, and numerous foods known to enhance or reduce its effects. Several disease states may also affect the pharmacologic activity of this drug. During warfarin therapy for VTE, the dose must be adjusted so that the international normalized ratio (INR) is kept above 2.0 to reduce thrombosis risk and below 3.0 to reduce bleeding risk. This narrow therapeutic window necessitates frequent laboratory monitoring and dose adjustment. Further complicating warfarin treatment is the variability in patient response to warfarin, and dosages must be carefully individualized.
Because of the many limitations of warfarin, much effort has been invested in the development of alternative oral drug therapies. Several new agents are in review or nearing review by the United States Food and Drug Administration. Given the large number of patients who require long-term anticoagulation, such as those with heritable conditions predisposing them to recurrent VTE or patients with atrial fibrillation, it is important for physicians to become familiar with these agents and some of the clinical evidence that supports their efficacy and safety profiles. |