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A Preliminary Assessment of the Critical Differences Between Novel Oral Anticoagulants Currently in Development

From Electrophysiologic and Metabolic Pharmacogenomics, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.

Chronic anticoagulation represents a clinical conundrum for the health care community that balances unquestionable morbidity and mortality benefits against interindividual variability, leading to drug interactions, adverse events, and thromoembolic events related to underdosing. Despite the growing data regarding the appropriate use and dosing of agents used for chronic anticoagulation, use in clinical practice remains low, thus leading to a theoretical reduction in the risk-to-benefit ratio in the clinical setting relative to that reported in the literature. Oral anticoagulants currently in development represent a heterogeneous group of compounds that are specific for the final common pathway in the coagulation cascade and show indications toward a reduced drug interaction profile, reduced interpatient variation in pharmacokinetic parameters, and morbidity and mortality benefits that might be similar to currently available treatment modalities. This review highlights the critical differences among oral anticoagulants in development and places their role in the context of the benefits and limitations of currently available anticoagulants.

Key Words: Anticoagulants • thrombin • factor Xa • razaxaban • ximelagatran

Address for reprints: Brian F. McBride, PharmD, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, 536 Robinson Research Building, Nashville, TN 37232.