Skip to main content

Advertisement

SpringerLink
Log in

Direct Oral Anticoagulants: An Overview for the Interventional Radiologist

  • Review
  • Published:
CardioVascular and Interventional Radiology Aims and scope Submit manuscript

Abstract

The direct oral anticoagulants (DOACs) have emerged as a good alternative for the treatment of thromboembolic diseases, and their use in clinical practice is increasing rapidly. The DOACs act by blocking the activity of one single step in the coagulation cascade. These drugs act downstream in the common pathway of the coagulation cascade by directly antagonising the action of thrombin or factor Xa. The development of DOACs represents a paradigm shift from the oral vitamin K antagonists such as warfarin. This article aims to describe the properties of the currently available DOACs including pharmacology and dosing. We also address the strategies for periprocedural management and reversal of anticoagulation of patients treated with these agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Mackman N. Triggers, targets and treatments for thrombosis. Nature. 2008;451:914–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, et al. Heart disease and stroke statistics—2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007;115:e69–171.

    Article  PubMed  Google Scholar 

  3. Douketis JD, Berger PB, Dunn AS, Jaffer AK, Spyropoulos AC, Becker RC, et al. The perioperative management of antithrombotic therapy *. CHEST J. 2008;133:299S.

    Article  CAS  Google Scholar 

  4. Patel IJ, Davidson JC, Nikolic B, Salazar GM, Schwartzberg MS, Walker TG, et al. Consensus guidelines for periprocedural management of coagulation status and hemostasis risk in percutaneous image-guided interventions. J Vasc Interv Radiol. 2012;23:727–36.

    Article  PubMed  Google Scholar 

  5. Barnes GD, Ageno W, Ansell J, Kaatz S, Husted S, Lip GYH, et al. Recommendation on the nomenclature for oral anticoagulants: communication from the SSC of the ISTH: comment. J Thromb Haemost. 2015;13:2130–2.

    Article  Google Scholar 

  6. Weitz JI. Anticoagulation therapy in 2015: where we are and where we are going. J Thromb Thrombolysis. 2015;39:264–72.

    Article  CAS  PubMed  Google Scholar 

  7. Camm AJ, Lip GYH, De Caterina R, Savelieva I, Atar D, Hohnloser SH, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33:2719–47.

    Article  PubMed  Google Scholar 

  8. Chan NC, Eikelboom JW, Weitz JI. Evolving treatments for arterial and venous thrombosis. Circ Res. 2016;118:1409–24.

    Article  CAS  PubMed  Google Scholar 

  9. Weinz C, Schwarz T, Kubitza D, Mueck W, Lang D. Metabolism and excretion of rivaroxaban, an oral, direct factor Xa inhibitor, in rats, dogs, and humans. Drug Metab Dispos. 2009;37:1056–64.

    Article  CAS  PubMed  Google Scholar 

  10. Frost C, Wang J, Nepal S, Schuster A, Barrett YC, Mosqueda-Garcia R, et al. Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects. Br J Clin Pharmacol. 2013;75:476–87.

    Article  CAS  PubMed  Google Scholar 

  11. Ogata K, Mendell-Harary J, Tachibana M, Masumoto H, Oguma T, Kojima M, et al. Clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel factor Xa inhibitor edoxaban in healthy volunteers. J Clin Pharmacol. 2010;50:743–53.

    Article  CAS  PubMed  Google Scholar 

  12. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47:285–95.

    Article  CAS  PubMed  Google Scholar 

  13. Chai-Adisaksopha C, Crowther M, Isayama T, Lim W, Kearon C, Gent M, et al. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood. 2014;124:2450–8.

    Article  CAS  PubMed  Google Scholar 

  14. Hart RG, Diener H-C, Yang S, Connolly SJ, Wallentin L, Reilly PA, et al. Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: the RE-LY trial. Stroke. 2012;43:1511–7.

    Article  CAS  PubMed  Google Scholar 

  15. Hylek EM, Held C, Alexander JH, Lopes RD, De Caterina R, Wojdyla DM, et al. Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin. J Am Coll Cardiol. 2014;63:2141–7.

    Article  PubMed  Google Scholar 

  16. Stangier J, Rathgen K, Stähle 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. 2007;64:292–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Blech S, Ebner T, Ludwig-Schwellinger E, Stangier J, Roth W, American Society for Pharmacology and Experimental Therapeutics. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos. 2008;36:386–99.

    Article  CAS  PubMed  Google Scholar 

  18. Hariharan S, Madabushi R. Clinical pharmacology basis of deriving dosing recommendations for dabigatran in patients with severe renal impairment. J Clin Pharmacol. 2012;52:119S–25S.

    Article  CAS  PubMed  Google Scholar 

  19. Wittkowsky AK. Novel oral anticoagulants and their role in clinical practice. Pharmacotherapy. 2011;31:1175–91.

  20. Stangier J, Rathgen K, Stähle 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. 2010;49:259–68.

    Article  CAS  PubMed  Google Scholar 

  21. Stampfuss J, Kubitza D, Becka M, Mueck W. The effect of food on the absorption and pharmacokinetics of rivaroxaban. Int J Clin Pharmacol Ther. 2013;51:549–61.

    Article  CAS  PubMed  Google Scholar 

  22. Mueck W, Schwers S, Stampfuss J. Rivaroxaban and other novel oral anticoagulants: pharmacokinetics in healthy subjects, specific patient populations and relevance of coagulation monitoring. Thromb J. 2013;11:1.

    Article  Google Scholar 

  23. Kubitza D, Becka M, Wensing G, Voith B, Zuehlsdorf M. Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939–an oral, direct factor Xa inhibitor–after multiple dosing in healthy male subjects. Eur J Clin Pharmacol. 2005;61:873–80.

    Article  CAS  PubMed  Google Scholar 

  24. Fox KAA, Piccini JP, Wojdyla D, Becker RC, Halperin JL, Nessel CC, et al. Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment. Eur Heart J. 2011;32:2387–94.

    Article  CAS  PubMed  Google Scholar 

  25. Martinelli I, Lensing AWA, Middeldorp S, Levi M, Beyer-Westendorf J, van Bellen B, et al. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use. Blood. 2016;127:1417–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wang L, Zhang D, Raghavan N, Yao M, Ma L, Frost CE, et al. In vitro assessment of metabolic drug-drug interaction potential of apixaban through cytochrome P450 phenotyping, inhibition, and induction studies. Drug Metab Dispos. 2010;38:448–58.

    Article  CAS  PubMed  Google Scholar 

  27. Acharya T, Deedwania P. An evidence-based review of edoxaban and its role in stroke prevention in patients with nonvalvular atrial fibrillation. Core Evid. 2015;10:63–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Matsushima N, Lee F, Sato T, Weiss D, Mendell J. Bioavailability and safety of the factor Xa inhibitor edoxaban and the effects of quinidine in healthy subjects. Clin Pharmacol Drug Dev. 2013;2:358–66.

    Article  CAS  PubMed  Google Scholar 

  29. Healey JS, Eikelboom J, Douketis J, Wallentin L, Oldgren J, Yang S, et al. Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the randomized evaluation of long-term anticoagulation therapy (RE-LY) randomized trial. Circulation. 2012;126:343–8.

    Article  CAS  PubMed  Google Scholar 

  30. Sherwood MW, Douketis JD, Patel MR, Piccini JP, Hellkamp AS, Lokhnygina Y, et al. Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from ROCKET AF. Circulation. 2014;129:1850–9. doi:10.1161/CIRCULATIONAHA.113.005754.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J. 2013;34(27):2094–106.

    Article  CAS  PubMed  Google Scholar 

  32. Baron TH, Kamath PS, McBane RD. Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med. 2013;368:2113–24.

    Article  CAS  PubMed  Google Scholar 

  33. Makris M, Van Veen JJ, Tait CR, Mumford AD, Laffan M. Guideline on the management of bleeding in patients on antithrombotic agents. Br J Haematol. 2013;160:35–46.

    Article  CAS  PubMed  Google Scholar 

  34. Schulman S. Advantages and limitations of the new anticoagulants. J Intern Med. 2014;275:1–11.

    Article  CAS  PubMed  Google Scholar 

  35. Hawes EM, Deal AM, Funk-Adcock D, Gosselin R, Jeanneret C, Cook AM, et al. Performance of coagulation tests in patients on therapeutic doses of dabigatran: a cross-sectional pharmacodynamic study based on peak and trough plasma levels. J Thromb Haemost. 2013;11:1493–502.

    Article  CAS  PubMed  Google Scholar 

  36. Becker RC, Yang H, Barrett Y, Mohan P, Wang J, Wallentin L, et al. Chromogenic laboratory assays to measure the factor Xa-inhibiting properties of apixaban—an oral, direct and selective factor Xa inhibitor. J Thromb Thrombolysis. 2011;32:183–7.

    Article  PubMed  Google Scholar 

  37. Beyer-Westendorf J, Gelbricht V, Förster K, Ebertz F, Köhler C, Werth S, et al. Peri-interventional management of novel oral anticoagulants in daily care: results from the prospective Dresden NOAC registry. Eur Heart J. 2014;35:1888–96.

    Article  CAS  PubMed  Google Scholar 

  38. Zhou W, Schwarting S, Illanes S, Liesz A, Middelhoff M, Zorn M, et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran. Stroke. 2011;42:3594–9.

    Article  PubMed  Google Scholar 

  39. Pragst I, Zeitler SH, Doerr B, Kaspereit FJ, Herzog E, Dickneite G, et al. Reversal of dabigatran anticoagulation by prothrombin complex concentrate (Beriplex P/N) in a rabbit model. J Thromb Haemost. 2016;10:1841–8.

    Article  Google Scholar 

  40. Zahir H, Brown KS, Vandell AG, Desai M, Maa J-F, Dishy V, et al. Edoxaban effects on bleeding following punch biopsy and reversal by a 4-factor prothrombin complex concentrate. Circulation. 2015;131:82–90.

    Article  CAS  PubMed  Google Scholar 

  41. Perlstein I, Wang Z, Song Y, Wang J, Bedford B, Chang M, American Society of Hematology, et al. Reversal of apixaban anticoagulation by 4-factor prothrombin complex concentrates in healthy subjects. Blood. 2014;124:345.

    Google Scholar 

  42. Escolar G, Fernandez-Gallego V, Arellano-Rodrigo E, Roquer J, Reverter JC, Sanz VV, et al. Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood. PLoS ONE. 2013;8:e78696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Levi M, Levy JH, Andersen HF, Truloff D. Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med. 2010;363:1791–800.

    Article  CAS  PubMed  Google Scholar 

  44. Schulman S, Crowther MA, Administration USF and D, Connolly S, Ezekowitz M, Yusuf S, et al. How I treat with anticoagulants in 2012: new and old anticoagulants, and when and how to switch. Blood. 2012;119:3016–23.

    Article  CAS  PubMed  Google Scholar 

  45. Douketis JD, Spyropoulos AC, Spencer FA, Mayr M, Jaffer AK, Eckman MH, et al. Perioperative management of antithrombotic therapy. Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141:e326S–50S.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Faraoni D, Levy JH, Albaladejo P, Samama C-M, Groupe d’Intérêt en Hémostase Périopératoire. Updates in the perioperative and emergency management of non-vitamin K antagonist oral anticoagulants. Crit Care. 2015;19:203.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Gould MK, Garcia DA, Wren SM, Karanicolas PJ, Arcelus JI, Heit JA, et al. Prevention of VTE in nonorthopedic surgical patients. Chest. 2012;141:e227S–77S.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Spyropoulos AC, Douketis JD. How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood. 2012;120:2954–62.

    Article  CAS  PubMed  Google Scholar 

  49. Majeed A, Hwang HG, Connolly SJ, Eikelboom JW, Ezekowitz MD, Wallentin L, et al. Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation. 2013;128(21):2325–32.

    Article  CAS  PubMed  Google Scholar 

  50. Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL, et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med. 2015;373:2413–24.

    Article  CAS  PubMed  Google Scholar 

  51. Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso M, Brown K, et al. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med. 2014;371:2141–2.

    Article  PubMed  Google Scholar 

  52. Martin K, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost. 2016;14:1308–13.

    Article  CAS  PubMed  Google Scholar 

  53. Vanassche T, Hirsh J, Eikelboom JW, Ginsberg JS. Organ-specific bleeding patterns of anticoagulant therapy: lessons from clinical trials. Thromb Haemost. 2014;112:918–23.

    Article  PubMed  Google Scholar 

  54. Raghavan N, Frost CE, Yu Z, He K, Zhang H, Humphreys WG, et al. Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos. 2009;37:74–81.

    Article  CAS  PubMed  Google Scholar 

  55. Bathala MS, Masumoto H, Oguma T, He L, Lowrie C, Mendell J. Pharmacokinetics, biotransformation, and mass balance of edoxaban, a selective, direct factor Xa inhibitor, in humans. Drug Metab Dispos. 2012;40:2250–5.

    Article  CAS  PubMed  Google Scholar 

  56. Kamath SD, McMahon BJ. Update on anticoagulation: what the interventional radiologist needs to know. Semin Interv Radiol. 2016;33(02):122–31.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Radiology Department, Aintree University Hospitals NHS Foundation Trust, Longmoor Lane, Liverpool, L9 7AL, UK

    Pradesh Kumar, Rajeev Ravi & Gaurav Sundar

  2. Haematology Department, Aintree University Hospitals NHS Foundation Trust, Longmoor Lane, Liverpool, L9 7AL, UK

    Caroline Shiach

Authors
  1. Pradesh Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rajeev Ravi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gaurav Sundar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Caroline Shiach
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pradesh Kumar.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author declares that they have no conflicts of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed Consent

Does not apply.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumar, P., Ravi, R., Sundar, G. et al. Direct Oral Anticoagulants: An Overview for the Interventional Radiologist. Cardiovasc Intervent Radiol 40, 321–330 (2017). https://doi.org/10.1007/s00270-016-1521-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00270-016-1521-0

Keywords

Search

Navigation