• Bruna Guimarães Faculty of Medicine, University of Porto, Porto
  • Luciana Ricca Gonçalves Serviço de Imunohemoterapia, Centro Hospitalar de São João, Faculdade de Medicina da Universidade do Porto, Porto
  • Armando Mansilha Serviço de Angiologia e Cirurgia Vascular, Centro Hospitalar de São João, Faculdade de Medicina da Universidade do Porto, Porto
Keywords: Direct oral anticoagulants, Deep vein thrombosis, Dabigatran, Rivaroxaban, Apixaban, Edoxaban


The deep vein thrombosis (DVT) is a high morbility pathology if not properly diagnosed and treated at its aerly stage. The direct oral anticoagulants (doacs), which selectly inhibit factor IIa (dabigatran) or factor Xa (rivaroxaban, apixaban and edoxaban), have become an attractive alternative to conventional therapy due to their fixed doses, no food interactions and absence of monitoring. 

The aim of this wrk is to procced with a revision on therapeutic use of DOACs and their risk/benefit correlation in comparison to conventional therapy in the DVT treatment and prevention. 

It was conducted a search on Pubmed database of English-language articles that addressed the DOACs in treatment and secondary prevention of DVT. It were also included the major cinica trials and the atest guidelines for the treatment and prevention of Venous Thromboembolism (VTE).

Large randomized studies sateted the non-inferiority of DOACs in the efficiency profile in comparison to conventional therapy, with the adventage of providing a higher safety profile. The improved risk/benefir ratio of DOACs combined with predictable pharmacokinetic properties and the absence of monitoring allow a better relation cost/efficiency.

Athough not all patients benefit from this therapy, which should be individualized in each case, the DOACs have changed DVT treatment and prevention into a more practical and safer procedure, associated with a higher patient satisfaction and a decrease in recurrent events incidence, lauching a new paradigm in DVT treatment and prevention.


1. Cushman, M. Treating Acute Venous Thromboembolism: Shift with Care. N. Engl. J. Med. 8–10 (2013). doi:10.1056/NEJMe1307413

2. K.M., B. et al. Deep vein thrombosis and novel oral anticoagulants: A clinical review. Eur. Rev. Med. Pharmacol. Sci. 17, 3123–3131 (2013).

3. Pascarella, L., Cox, M. W. & O’Brien, P. J. Venous thromboembolism: diagnosis and current anticoagulation strategies for deep vein thrombosis and pulmonary embolism. Hosp. Pract. (1995) 40, 58–70 (2012).

4. Thaler, J., Pabinger, I. & Ay, C. Anticoagulant Treatment of Deep Vein Thrombosis and Pulmonary Embolism: The Present State of the Art. Front. Cardiovasc. Med. 2, 30 (2015).

5. Wang, P., Song, C. & Jin, Y. Antithrombotic Therapy for VTE Disease: CHEST Guideline. Chest 7–20 (2016). doi:10.1016/j. physa.2010.10.017

6. Fontana, P., Goldhaber, S. Z. & Bounameaux, H. Direct oral anticoagulants in the treatment and long-term prevention of venous thrombo-embolism. Eur. Heart J. 35, 1836–1843 (2014).

7. Kearon, C. et al. Antithrombotic therapy for VTE disease: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 141, 419–494 (2012).

8. Yeh, C. H., Hogg, K. & Weitz, J. I. Overview of the New Oral Anticoagulants: Opportunities and Challenges. Arterioscler. Thromb. Vasc. Biol. 1–11 (2015). doi:10.1161/ATVBAHA.115.303397

9. Chin, P. K. L. Which patients may benefit from dose adjustment of non-vitamin k antagonist oral anticoagulants? Semin. Thromb. Hemost. 41, 195–207 (2015).

10. Tideman, P. A., Tirimacco, R., St. John, A. & Roberts, G. W. How to manage warfarin therapy. Aust. Prescr. 38, 44–48 (2015).

11. Witt, D. M., Clark, N. P., Kaatz, S., Schnurr, T. & Ansell, J. E. Guidance for the practical management of warfarin therapy in the treatment of venous thromboembolism. J. Thromb. Thrombolysis 41, 187–205 (2016).

12. Feuring, M. & van Ryn, J. The discovery of dabigatran etexilate for the treatment of venous thrombosis. Expert Opin. Drug Discov. 11, 717–731 (2016).

13. Fanola, C. L. Current and emerging strategies in the management of venous thromboembolism: benefit-risk assessment of dabigatran. Vasc Heal. Risk Manag 11, 271–282 (2015).

14. Brown, R., Lip, G. Y. H. & Gallego, P. Dabigatran etexilate for venous thromboembolism: A safety evaluation. Expert Opin. Drug Saf. 13, 639–647 (2014).

15. Schulman, S. et al. Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism. N. Engl. J. Med. 361, 2342–2352 (2009).

16. Fontana, P., Robert-Ebadi, H., Bounameaux, H., Boehlen, F. & Righini, M. Direct oral anticoagulants: a guide for daily practice. Swiss Med. Wkly. 146, w14286 (2016).

17. Liem, T. K. & DeLoughery, T. G. Direct thrombin inhibitors for the treatment of venous thromboembolism: Analysis of the dabigatran versus warfarin clinical trial. Semin. Vasc. Surg. 24, 157–161 (2011).

18. Schulman, S. et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N. Engl. J. Med. 368, 709–18 (2013).

19. 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).

20. Arcelus, J. I. et al. Rivaroxaban in the treatment of venous thromboembolism and the prevention of recurrences: a practical approach. Clin. Appl. Thromb. Hemost. 21, 297–308 (2015).

21. Imberti, D. & Benedetti, R. Practical management of rivaroxaban for the treatment of venous thromboembolism. Clin. Appl. Thromb. Hemost. 21, 309–18 (2015).

22. Bauersachs, R. et al. Oral rivaroxaban for symptomatic venous thromboembolism. N. Engl. J. Med. 363, 2499–2510 (2010).

23. Trujillo, T. & Dobesh, P. P. Clinical Use of Rivaroxaban: Pharmacokinetic and pharmacodynamic rationale for dosing regimens in different indications. Drugs 74, 1587–1603 (2014).

24. Prins, M. H. et al. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb. J. 11, 21 (2013).

25. Mandernach, M. W., Beyth, R. J. & Rajasekhar, A. Apixaban for the prophylaxis and treatment of deep vein thrombosis and pulmonary embolism: An evidence-based review. Ther. Clin. Risk Manag. 11, 1273–1282 (2015).

26. Adamantia, L. & Antoni, T. Pharmacodynamics, pharmacokinetics and clinical efficacy of apixaban in the treatment of thrombosis. Expert Opin. Drug Metab. Toxicol. 5255, (2016).

27. Holy, E. W. & Beer, J. H. Direct Oral Anticoagulants in the Management of Venous Thromboembolism-Evidence From Major Clinical Trials. Semin. Hematol. 51, 131–138 (2014).

28. Curto, M. et al. Oral apixaban for the treatment of acute venous thromboembolism. Zeitschrift fur Gefassmedizin 10, 25–26 (2013).

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

30. Shirley, M. & Dhillon, S. Edoxaban: A Review in Deep Vein Thrombosis and Pulmonary Embolism. Drugs 75, 2025–2034 (2015).

31. Bounameaux, H. & Camm, A. J. Edoxaban: An update on the new oral direct factor Xa inhibitor. Drugs 74, 1209–1231 (2014).

32. Escolar, G., Diaz-Ricart, M., Arellano-Rodrigo, E. & Galán, A. M. The pharmacokinetics of edoxaban for the prevention and treatment of venous thromboembolism. Expert Opin. Drug Metab. Toxicol. 10, 445–458 (2014).

33. Raskob, G. et al. Edoxaban for the long-term treatment of venous thromboembolism: Rationale and design of the Hokusai-venous thromboembolism study - methodological implications for clinical trials. J. Thromb. Haemost. 11, 1287–1294 (2013).

34. Investigators, T. H.-V. Edoxanban versus Warfarin for the Treatment of Symptomatic Venous Thromboembolism. N. Engl. J. Med. 369, 1406–1415 (2013).

35. Lelonek, M., Ciurus, T., Sobczak, S., Cichocka-Radwan, A. & Lelonek, M. New oral anticoagulants – a practical guide. Kardiochirurgia i Torakochirurgia Pol. Torakochirurgia Pol. 12, 111–118 (2015).

36. Weitz, J. I. & Eikelboom, J. W. Urgent Need to Measure Effects of Direct Oral Anticoagulants: Table. Circulation 134, 186–188 (2016).

37. Heidbuchel, H. et al. Updated European Heart Rhythm Association Practical Guide on the use of non-Vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 17, 1467–1507 (2015).

38. Peacock, W. F. Managing bleeding and emergency reversal of newer oral anticoagulants: a review for primary care providers. Hosp. Pract. (1995) 42, 75–82 (2014).

39. Toth, P. P. Considerations for long-term anticoagulant therapy in patients with venous thromboembolism in the novel oral anticoagulant era. Vasc. Health Risk Manag. 12, 23–34 (2016).40. Samuelson, B. T. & Cuker, A. Measurement and reversal of the direct oral anticoagulants. Blood Rev. (2016). doi:10.1016/j.blre.2016.08.006

41. Pollack, C. V et al. Idarucizumab for Dabigatran Reversal. N. Engl. J. Med. 1–10 (2015). doi:10.1056/NEJMoa1502000

42. Siegal, D. M. et al. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N. Engl. J. Med. 373, 2413 –2424 (2015).

43. Connolly, S. J. et al. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. N. Engl. J. Med. NEJMoa1607887 (2016). doi:10.1056/NEJMoa1607887

44. Treschan, T. A. & Beiderlinden, M. Antidotes for anticoagulants: A long way to go. Lancet 386, 634–636 (2015).

45. Faraoni, D., Levy, J. H., Albaladejo, P. & Samama, C.-M. Updates in the perioperative and emergency management of non-vitamin K antagonist oral anticoagulants. Crit. Care 19, 203 (2015).

46. Lugthart, S. & Leebeek, F. W. Direct oral anticoagulants: To switch or not to switch? Neth. J. Med. 73, 359–361 (2015).

47. Roca, B. & Roca, M. The new oral anticoagulants: Reasonable alternatives to warfarin. Cleve. Clin. J. Med. 82, 847–854 (2015).

48. Bauer, K. a. Pros and cons of new oral anticoagulants. Hematology Am. Soc. Hematol. Educ. Program 2013, 464–70 (2013).

49. Gómez-Outes, A., Suárez-Gea, M. L., Lecumberri, R., Terleira-Fernández, A. I. & Vargas-Castrillón, E. Direct oral anticoagulants in the treatment of venous thromboembolism, with a focus on patients with pulmonary embolism: an evidence-based review. Vasc. Health Risk Manag. 10, 627–39 (2014).
Review Article