Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

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

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

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

Similar content being viewed by others

References

  1. Steffel, J., Luscher, T. F. & Tanner, F. C. Tissue factor in cardiovascular diseases: molecular mechanisms and clinical implications. Circulation 113, 722–731 (2006).

    Article  CAS  PubMed  Google Scholar 

  2. Hart, R. G., Pearce, L. A. & Aguilar, M. I. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann. Intern. Med. 146, 857–867 (2007).

    Article  PubMed  Google Scholar 

  3. Guyatt, G. H. et al. Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 141 (Suppl. 2), 7S–47S (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Steffel, J. & Luscher, T. F. Vitamin K antagonists: ready to be replaced? Hamostaseologie 32, 249–257 (2012).

    Article  CAS  PubMed  Google Scholar 

  5. Giorgi, M. A., Cohen Arazi, H., Gonzalez, C. D. & Di Girolamo, G. Changing anticoagulant paradigms for atrial fibrillation: dabigatran, apixaban and rivaroxaban. Expert Opin. Pharmacother. 12, 567–577 (2011).

    Article  CAS  PubMed  Google Scholar 

  6. Harder, S., Parisius, J. & Picard-Willems, B. Monitoring direct FXa-inhibitors and fondaparinux by prothrombinase-induced clotting time (PiCT): relation to FXa-activity and influence of assay modifications. Thromb. Res. 123, 396–403 (2008).

    Article  CAS  PubMed  Google Scholar 

  7. Brenner, B. & Hoffman, R. Emerging options in the treatment of deep vein thrombosis and pulmonary embolism. Blood Rev. 25, 215–221 (2011).

    Article  CAS  PubMed  Google Scholar 

  8. Blech, S., Ebner, T., Ludwig–Schwellinger, E., Stangier, J. & Roth, W. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab. Dispos. 36, 386–399 (2008).

    Article  CAS  PubMed  Google Scholar 

  9. Stangier, J., Rathgen, K., Stahle, H. & Mazur, D. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin. Pharmacokinet. 49, 259–268 (2010).

    Article  CAS  PubMed  Google Scholar 

  10. Stangier, J., Rathgen, K., Stahle, H., Gansser, D. & Roth, W. The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. Br. J. Clin. Pharmacol. 64, 292–303 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. van Ryn, J. et al. Dabigatran etexilate—a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb. Haemost. 103, 1116–1127 (2010).

    Article  CAS  PubMed  Google Scholar 

  12. Schulman, S. et al. A randomized trial of dabigatran versus warfarin in the treatment of acute venous thromboembolism (RE-COVER II) [abstract 205]. Presented at the American Society of Hematology 2011 Annual Meeting.

  13. Eriksson, B. I. et al. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J. Thromb. Haemost. 5, 2178–2185 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. RE-MOBILIZE Writing Committee et al. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J. Arthroplasty 24, 1–9 (2009).

  15. Eriksson, B. I. et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 370, 949–956 (2007).

    Article  CAS  PubMed  Google Scholar 

  16. Eriksson, B. I. et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*): a randomised, double-blind, non-inferiority trial. Thromb. Haemost. 105, 721–729 (2011).

    Article  CAS  PubMed  Google Scholar 

  17. Schulman, S. et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N. Engl. J. Med. 361, 2342–2352 (2009).

    Article  CAS  PubMed  Google Scholar 

  18. Prandoni, P. & Taher, A. Insights from the dabigatran versus warfarin trial in patients with venous thromboembolism (the RE-COVER trial). Expert Opin. Pharmacother. 11, 1035–1037 (2010).

    Article  CAS  PubMed  Google Scholar 

  19. Schulman, S. et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N. Engl. J. Med. 368, 709–718 (2013).

    Article  CAS  PubMed  Google Scholar 

  20. Dans, A. L. et al. Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Circulation 127, 634–640 (2013).

    Article  CAS  PubMed  Google Scholar 

  21. Uchino, K. & Hernandez, A. V. Dabigatran association with higher risk of acute coronary events: meta-analysis of noninferiority randomized controlled trials. Arch. Intern. Med. 172, 397–402 (2012).

    Article  CAS  PubMed  Google Scholar 

  22. Perzborn, E. et al. Rivaroxaban: a new oral factor Xa inhibitor. Arterioscler. Thromb. Vasc. Biol. 30, 376–381 (2010).

    Article  CAS  PubMed  Google Scholar 

  23. Baumann Kreuziger, L. M., Morton, C. T. & Dries, D. J. New anticoagulants: a concise review. J. Trauma Acute Care Surg. 73, 983–992 (2012).

    Article  CAS  PubMed  Google Scholar 

  24. Eriksson, B. I. et al. Rivaraoxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N. Engl. J. Med. 388, 2765–2775 (2008).

    Article  Google Scholar 

  25. Kakkar, A. K. et al. Extended duration rivaroxaban versus short term enoxaparin for the prevention of VTE after total hip arthroplasty. Lancet 372, 31–39 (2008).

    Article  CAS  PubMed  Google Scholar 

  26. Lassen, M. R. et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N. Engl. J. Med. 358, 2776–2786 (2008).

    Article  CAS  PubMed  Google Scholar 

  27. Turpie, A. G. et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomized trial. Lancet 373, 1673–1680 (2009).

    Article  CAS  PubMed  Google Scholar 

  28. Turun, S. et al. A systematic review of rivaroxaban versus enoxaparin in the prevention of venous thromboembolism after hip or knee replacement. Thromb. Res. 127, 525–534 (2011).

    Article  PubMed  Google Scholar 

  29. Cohen, A. T. et al. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N. Engl. J. Med. 368, 513–523 (2013).

    Article  CAS  PubMed  Google Scholar 

  30. Raghavan, N. et al. Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab. Dispos. 37, 74–81 (2009).

    Article  CAS  PubMed  Google Scholar 

  31. EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N. Engl. J. Med. 363, 2499–2510 (2010).

  32. EINSTEIN-PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N. Engl. J. Med. 366, 1287–1297 (2012).

  33. Prandoni, P. Anticoagulant treatment of pulmonary embolism: impact and implications of the EINSTEIN PE study. Eur. J. Haematol. 89, 281–287 (2012).

    Article  CAS  PubMed  Google Scholar 

  34. Romualdi, E., Donadini, M. P. & Ageno, W. Oral rivaroxaban after symptomatic venous thromboembolism: the continued treatment study (EINSTEIN-extension study). Expert Rev. Cardiovasc. Ther. 9, 841–844 (2011).

    Article  CAS  PubMed  Google Scholar 

  35. Lassen, M. R. et al. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N. Engl. J. Med. 361, 594–604 (2009).

    Article  CAS  PubMed  Google Scholar 

  36. Lassen, M. R. et al. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet 375, 807–815 (2010).

    Article  CAS  PubMed  Google Scholar 

  37. Lassen, M. R. et al. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N. Engl. J. Med. 363, 2487–2498 (2010).

    Article  CAS  PubMed  Google Scholar 

  38. Goldhaber, S. Z. et al. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N. Engl. J. Med. 365, 2167–2177 (2011).

    Article  CAS  PubMed  Google Scholar 

  39. US National Library of Medicine. ClinicalTrials.gov [online], (2012).

  40. Agnelli, G. et al. Apixaban for extended treatment of venous thromboembolism. N. Engl. J. Med. 368, 699–708 (2013).

    Article  CAS  PubMed  Google Scholar 

  41. Ruff, C. T. et al. Evaluation of the novel factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation: design and rationale for the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation-Thrombolysis In Myocardial Infarction study 48 (ENGAGE AF-TIMI 48). Am. Heart J. 160, 635–641 (2010).

    Article  CAS  PubMed  Google Scholar 

  42. Raskob, G. et al. Edoxaban for the long-term treatment of venous thromboembolism: rationale and design of the Hokusai-VTE study. J. Thromb. Haemost. http://dx.doi.org/10.1111/jth.12230.

  43. Yeh, C. H., Fredenburgh, J. C. & Weitz, J. I. Oral direct factor Xa inhibitors. Circ. Res. 111, 1069–1078 (2012).

    Article  CAS  PubMed  Google Scholar 

  44. Fuji, T., Fujita, S., Tachibana, S. & Kawai, Y. Edoxaban versus enoxaparin for the prevention of venous thromboembolism and bleeding from STARS E-3 and STARS J.-V [abstract 208]. Presented at the American Society of Hematology 2011 Annual Meeting.

  45. Ahrens, I. & Bode, C. Oral anticoagulation with edoxaban. Focus on current phase III clinical development. Hamostaseologie 32, 212–215 (2012).

    Article  CAS  PubMed  Google Scholar 

  46. Raskob, G. et al. Oral direct factor Xa inhibition with edoxaban for thromboprophylaxis after elective total hip replacement: a randomised double-blind dose-response study. Thromb. Haemost. 104, 642–649 (2010).

    Article  CAS  PubMed  Google Scholar 

  47. Fuji, T. et al. A dose-ranging study evaluating the oral factor Xa inhibitor edoxaban for prevention of venous thromboembolism in patients undergoing total knee arthroplasty. J. Thromb. Haemost. 8, 2458–2468 (2010).

    Article  CAS  PubMed  Google Scholar 

  48. Piazza, G. et al. Venous thromboembolism in patients with symptomatic atherosclerosis. Thromb. Haemost. 106, 1095–1102 (2011).

    Article  CAS  PubMed  Google Scholar 

  49. Piazza, G. et al. Venous thromboembolism in patients with diabetes mellitus. Am. J. Med. 125, 709–716 (2011).

    Article  Google Scholar 

  50. Prandoni, P. et al. An association between atherosclerosis and venous thrombosis. N. Engl. J. Med. 348, 1435–1441 (2003).

    Article  PubMed  Google Scholar 

  51. Prandoni, P. Venous thromboembolism and atherosclerosis: is there a link? J. Thromb. Haemost. 5 (Suppl. 1), 270–275 (2007).

    Article  CAS  PubMed  Google Scholar 

  52. Prandoni, P. Links between arterial and venous disease. J. Intern. Med. 262, 341–350 (2007).

    Article  CAS  PubMed  Google Scholar 

  53. O'Gara, P. T. et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Circulation 127, e362–e425 (2013).

    PubMed  Google Scholar 

  54. Fiessinger, J. N. et al. Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: a randomized trial. JAMA 293, 681–689 (2005).

    Article  CAS  PubMed  Google Scholar 

  55. Olsson, S. B. et al. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial. Lancet 362, 1691–1968 (2003).

    Article  CAS  PubMed  Google Scholar 

  56. Albers, G. W. et al. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA 293, 690–698 (2005).

    Article  PubMed  Google Scholar 

  57. Artang, R., Rome, E. & Vidaillet, H. Dabigatran and myocardial infarction, drug or class effect: meta-analysis of randomized trials with oral direct thrombin inhibitors [abstract]. J. Am. Coll. Cardiol. 59, E571 (2012).

    Article  Google Scholar 

  58. Komocsi, A., Vorobcsuk, A., Kehl, D. & Aradi, D. Use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an acute coronary syndrome: systematic review and meta-analysis of randomized controlled trials. Arch. Intern. Med. 172, 1537–1545 (2012).

    Article  PubMed  Google Scholar 

  59. Thomas, K. A promising drug with a flaw. The New York Times (2 November 2012).

  60. Eerenberg, E. S. et al. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation 124, 1573–1579 (2011).

    Article  CAS  PubMed  Google Scholar 

  61. Crowther, M. A. & Warkentin, T. E. Managing bleeding in anticoagulated patients with a focus on novel therapeutic agents. J. Thromb. Haemost. 7 (Suppl. 1), 107–110 (2009).

    Article  CAS  PubMed  Google Scholar 

  62. Marlu, R. et al. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb. Haemost. 108, 217–224 (2012).

    Article  CAS  PubMed  Google Scholar 

  63. van Ryn, J. et al. Dabigatran etexilate—a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb. Haemost. 103, 1116–1127 (2010).

    Article  CAS  PubMed  Google Scholar 

  64. Akwaa, F. & Spyropoulos, A. C. Treatment of bleeding complications when using oral anticoagulants for prevention of strokes. Curr. Treat. Options Cardiovasc. Med. http://dx.doi.org/10.1007/s11936-013-0238-5.

  65. Godier, A. et al. Evaluation of prothrombin complex concentrate and recombinant activated factor VII to reverse rivaroxaban in a rabbit model. Anesthesiology 116, 94–102 (2012).

    Article  CAS  PubMed  Google Scholar 

  66. Hollenbach, S. J. et al. PRT064445 but not recombinant FVIIa reverses rivaroxaban induced anticoagulation as measured by reduction in blood loss in a rabbit liver laceration model [abstract 3414]. Presented at the American Society of Hematology 2012 Annual Meeting.

  67. Kaatz, S. et al. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am. J. Hematol. 87 (Suppl. 1), S141–S145 (2012).

    Article  CAS  PubMed  Google Scholar 

  68. Samama, M. M. et al. Assessment of laboratory assays to measure rivaroxaban—an oral, direct factor Xa inhibitor. Thromb. Haemost. 103, 815–825 (2010).

    Article  CAS  PubMed  Google Scholar 

  69. Poulsen, B. K., Grove, E. L. & Husted, S. E. New oral anticoagulants: a review of the literature with particular emphasis on patients with impaired renal function. Drugs 72, 1739–1753 (2012).

    Article  CAS  PubMed  Google Scholar 

  70. Baber, U., van der Zee, S. & Fuster, V. Anticoagulation for mechanical heart valves in patients with and without atrial fibrillation. Curr. Cardiol. Rep. 12, 133–139 (2010).

    Article  PubMed  Google Scholar 

  71. Price, J., Hynes, M., Labinaz, M., Ruel, M. & Boodhwani, M. Mechanical valve thrombosis with dabigatran. J. Am. Coll. Cardiol. 60, 1710–1711 (2012).

    Article  PubMed  Google Scholar 

  72. Van de Werf, F. et al. A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: the randomized, phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement (RE-ALIGN). Am. Heart J. 163, 931–937, e1 (2012).

    Article  CAS  PubMed  Google Scholar 

  73. Heit, J. A. et al. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann. Intern. Med. 143, 697–706 (2005).

    Article  PubMed  Google Scholar 

  74. James, A. H., Jamison, M. G., Brancazio, L. R. & Myers, E. R. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. Am. J. Obstet. Gynecol. 194, 1311–1315 (2006).

    Article  PubMed  Google Scholar 

  75. Forestier, F., Daffos, F. & Capella-Pavlovsky, M. Low molecular weight heparin (PK 10169) does not cross the placenta during the second trimester of pregnancy study by direct fetal blood sampling under ultrasound. Thromb. Res. 34, 557–560 (1984).

    Article  CAS  PubMed  Google Scholar 

  76. Ginsberg, J. S., Hirsh, J., Turner, D. C., Levine, M. N. & Burrows, R. Risks to the fetus of anticoagulant therapy during pregnancy. Thromb. Haemost. 61, 197–203 (1989).

    Article  CAS  PubMed  Google Scholar 

  77. Romualdi, E. et al. Anticoagulant therapy for venous thromboembolism during pregnancy: a systematic review and a meta-analysis of the literature. J. Thromb. Haemost. 11, 270–281 (2013).

    Article  CAS  PubMed  Google Scholar 

  78. Jacobsen, A. F. & Sandset, P. M. Venous thromboembolism associated with pregnancy and hormonal therapy. Best Pract. Res. Clin. Haematol. 25, 319–332 (2012).

    Article  PubMed  Google Scholar 

  79. Stone, S. E. & Morris, T. A. Pulmonary embolism during and after pregnancy. Crit. Care Med. 33 (Suppl. 10), S294–S300 (2005).

    Article  PubMed  Google Scholar 

  80. Sorensen, H. T., Mellemkjaer, L., Olsen, J. H. & Baron, J. A. Prognosis of cancers associated with venous thromboembolism. N. Engl. J. Med. 343, 1846–1850 (2000).

    Article  CAS  PubMed  Google Scholar 

  81. Chew, H. K., Wun, T., Harvey, D., Zhou, H. & White, R. H. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch. Intern. Med. 166, 458–464 (2006).

    Article  PubMed  Google Scholar 

  82. Kuderer, N. M., Ortel, T. L. & Francis, C. W. Impact of venous thromboembolism and anticoagulation on cancer and cancer survival. J. Clin. Oncol. 27, 4902–11 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Horsted, F., West, J. & Grainge, M. J. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med. 9, e1001275 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Young, A. et al. Thrombosis and cancer. Nat. Rev. Clin. Oncol. 9, 437–449 (2012).

    Article  CAS  PubMed  Google Scholar 

  85. Lyman, G. H. et al. American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J. Clin. Oncol. 25, 5490–5505 (2007).

    Article  CAS  PubMed  Google Scholar 

  86. Lee, A. Y. et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N. Engl. J. Med. 349, 146–153 (2003).

    Article  CAS  PubMed  Google Scholar 

  87. Verso, M. & Agnelli, G. New and old anticoagulants in cancer. Thromb. Res. 129 (Suppl. 1), S101–S105 (2012).

    Article  CAS  PubMed  Google Scholar 

  88. Farge, D. et al. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J. Thromb. Haemost. 11, 56–70 (2013).

    Article  CAS  PubMed  Google Scholar 

  89. Levine, M. N. New antithrombotic drugs: potential for use in oncology. J. Clin. Oncol. 27, 4912–4918 (2009).

    Article  CAS  PubMed  Google Scholar 

  90. Turpie, A. G. et al. A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT). Thromb. Haemost. 101, 68–76 (2009).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed substantially to researching data for the article, discussion of content, wrote the article, and reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Joe F. Lau.

Ethics declarations

Competing interests

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.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrcardio.2013.73

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing