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Oral anticoagulants in the management of venous thromboembolism

Abstract

Despite advances in diagnosis, prevention, and management, venous thromboembolism (VTE) remains a common cause of morbidity and mortality. For decades, antithrombotic therapy for prevention and treatment of VTE was limited to parenteral agents related to heparin and oral vitamin K antagonists (VKAs). Both classes of anticoagulants are effective, but have limitations, including considerable variability in dose–response, narrow therapeutic margins between the risks of thrombosis and bleeding, and the need to monitor anticoagulation intensity. Over the past decade, the introduction of new oral anticoagulants that specifically inhibit coagulation factors IIa (thrombin) or Xa has changed practice in a variety of clinical situations, including VTE prophylaxis and treatment. In this Review, we outline the use of the novel oral anticoagulants apixaban, dabigatran, edoxaban, and rivaroxaban in the prevention and treatment of VTE, and discuss practical considerations for choosing the appropriate drug for each patient. Although the introduction of novel anticoagulant drugs is promising, selecting the optimum strategy for an individual patient requires an understanding of the specific circumstances associated with thrombus formation and the pharmacological properties of each agent.

Key Points

  • Vitamin K antagonists (VKAs), such as warfarin, are the mainstay of the management of venous thromboembolism (VTE)

  • The logistical difficulties associated with the use of VKAs include a narrow therapeutic window, unpredictable pharmacodynamics, and the need for routine monitoring; novel oral anticoagulants address some of these concerns

  • Novel anticoagulants include direct thrombin inhibitors, such as dabigatran, and factor Xa inhibitors such as apixaban, edoxaban, and rivaroxaban

  • Novel anticoagulants are in various stages of approval in the USA and Europe for several indications, including stroke prevention in atrial fibrillation, and the prophylaxis and treatment of VTE

  • The inability to quickly reverse or properly monitor the effects of the novel anticoagulants must be considered in the clinician's decision-making algorithm

  • The results of randomized trials will continue to clarify the role of these new agents in the management and prevention of VTE events

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Figure 1: Coagulation cascade and point of effect of the common oral anticoagulants.

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J. L. Halperin declares that he is or has been a consultant for Bayer AG Healthcare, Biotronik, Boehringer Ingelheim, Daiichi Sankyo, Johnson & Johnson, Ortho–McNeil–Janssen Pharmaceuticals, and Sanofi–Aventis. He also declares that he served as Chairman of the Data and Safety Monitoring Committee for a clinical trial sponsored by AstraZeneca.

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Makaryus, J., Halperin, J. & Lau, J. Oral anticoagulants in the management of venous thromboembolism. Nat Rev Cardiol 10, 397–409 (2013). https://doi.org/10.1038/nrcardio.2013.73

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