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CardioVascular and Interventional Radiology
Published in: CardioVascular and Interventional Radiology 3/2017

01-03-2017 | Review

Direct Oral Anticoagulants: An Overview for the Interventional Radiologist

Authors: Pradesh Kumar, Rajeev Ravi, Gaurav Sundar, Caroline Shiach

Published in: CardioVascular and Interventional Radiology | Issue 3/2017

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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.
Literature
1.
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.CrossRefPubMed
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.CrossRef
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.CrossRefPubMed
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.CrossRef
6.
Weitz JI. Anticoagulation therapy in 2015: where we are and where we are going. J Thromb Thrombolysis. 2015;39:264–72.CrossRefPubMed
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.CrossRefPubMed
8.
Chan NC, Eikelboom JW, Weitz JI. Evolving treatments for arterial and venous thrombosis. Circ Res. 2016;118:1409–24.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
12.
Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47:285–95.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRef
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.PubMedPubMedCentral
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.CrossRefPubMed
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.CrossRefPubMed
30.
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.CrossRefPubMed
32.
Baron TH, Kamath PS, McBane RD. Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med. 2013;368:2113–24.CrossRefPubMed
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.CrossRefPubMed
34.
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRef
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.CrossRefPubMed
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.
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMedPubMedCentral
48.
Spyropoulos AC, Douketis JD. How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood. 2012;120:2954–62.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
56.
Kamath SD, McMahon BJ. Update on anticoagulation: what the interventional radiologist needs to know. Semin Interv Radiol. 2016;33(02):122–31.CrossRef
Metadata
Title
Direct Oral Anticoagulants: An Overview for the Interventional Radiologist
Authors
Pradesh Kumar
Rajeev Ravi
Gaurav Sundar
Caroline Shiach
Publication date
01-03-2017
Publisher
Springer US
Published in
CardioVascular and Interventional Radiology / Issue 3/2017
Print ISSN: 0174-1551
Electronic ISSN: 1432-086X
DOI
https://doi.org/10.1007/s00270-016-1521-0

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