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Current Rheumatology Reports
Published in: Current Rheumatology Reports 6/2013

01-06-2013 | ANTIPHOSPHOLIPID SYNDROME (RAS ROUBEY, SECTION EDITOR)

Use of New Oral Anticoagulants in Antiphospholipid Syndrome

Authors: Deepa Jayakody Arachchillage, Hannah Cohen

Published in: Current Rheumatology Reports | Issue 6/2013

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Abstract

The current mainstay of treatment of thrombotic APS is long-term anticoagulation with oral vitamin K antagonists (VKA) such as warfarin. However, the use of warfarin is problematic, particularly in patients with antiphospholipid syndrome (APS). The new oral anticoagulants (NOAC) include dabigatran etexilate (Pradaxa®), a direct thrombin inhibitor, and rivaroxaban (Xarelto®), Apixaban (Eliquis) and Edoxaban (Lixiana®), which are direct anti-Xa inhibitors. Unlike warfarin, these agents do not interact with dietary constituents and alcohol, have few reported drug interactions, and monitoring of their anticoagulant intensity is not routinely required due to their predictable anticoagulant effects. In this chapter, we discuss clinical and laboratory aspects of NOAC. These agents have been approved for several therapeutic indications based on phase III prospective randomised controlled clinical trials using warfarin at a target INR of 2.5 (i.e. range 2.0–3.0) as the comparator. However these trials may not be directly applicable to patients with antiphospholipid syndrome (APS) where prospective clinical studies of NOAC are the way forward.
Literature
1.
Miyakis S, Lockshin MD, Atsumi D, et al. International consensus statement on an update of the preliminary classification criteria for antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295–306.PubMedCrossRef
2.
3.
Kearon C, Akl EA, Comerota AJ, 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. 2012;141(2 Suppl):e419S–94S.PubMedCrossRef
4.
Keeling D et al. British Committee for Standards in Haematology (BCSH) - Guidelines for General Haematology, Haemostasis and Thrombosis. Guidelines on oral anticoagulation with warfarin fourth edition. Br J Haematol. 2011;154:311–24.PubMedCrossRef
5.
Ruiz-Irastorza G, Crowther M, Branch W, Khamashta M. Antiphospholipid syndrome. Lancet. 2010;376:1498–509.PubMedCrossRef
6.
7.
Xarelto 10 mg film-coated tablets. Summary of product characteristics (SPC), EU. Bayer HealthCare AG. Date of first authorisation/renewal of authorisation: 30/09/08. Date of revision 12/2011. Available from: www.​emc.​medicines.​org.​uk.
8.
Connolly SJ, Ezekowitz MD, Yusuf S, et al. RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.PubMedCrossRef
9.
Patel MR, Mahaffey KW, Gar J, Pan G, Singe DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation (and supplementary appendix). N Engl J Med. 2011;365:883–91.PubMedCrossRef
10.
Committee for Medicinal Products for Human Use (CHMP), European Medicines Agency 26/07/2012 Pradaxa -EMEA/H/C/000829 -II/0032.
11.
Committee for Medicinal Products for Human Use (CHMP), European Medicines Agency. 09/12/2011 Xarelto -EMEA/H/C/000944 -X/0010.
12.
13.
NICE technology appraisal guidance 256. Rivaroxaban for the prevention of stroke and systemic embolism in people with atrial fibrillation.May 2012. www.​nice.​org.​uk/​TA 256.
14.
Erikkson BI, Dahl OE, Rosencher N, RE-MODEL Study Group, 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. 2007;5:2178–85.CrossRef
15.
Eriksson BI, Dahl OE, Rosencher N, RE-NOVATE Study group, et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet. 2007;370:949–56.PubMedCrossRef
16.
Eriksson BI, Borris LC, Dahl OE, RECORD 2 Investigators, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl JMed. 2008;358:2765–75.CrossRef
17.
Kakkar AK, Brenner B, Dahl OE, RECORD 2 Investigators, et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind randomised controlled trial. Lancet. 2008;372:31–9.PubMedCrossRef
18.
Lassen MR, Ageno W, Borris LC, RECORD 3 Investigators, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008;358:2776–86.PubMedCrossRef
19.
Turpie AG, Lassen MR, Davidson BL, RECORD 4 Investigators, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee replacement (RECORD 4): a randomised trial. Lancet. 2009;373:1673–80.PubMedCrossRef
20.
Eriksson BI, Quinlan DJ, Eikelboom JW. Novel Oral Factor Xa and Thrombin Inhibitors in the Management of Thromboembolism. Annu Rev Med. 2011;62:41–57.PubMedCrossRef
21.
Frost C, Yu Z, Nepal S, Mosqueda-Garcia R, Shenker A. Apixaban, an oral direct, factor Xa inhibitor: multiple ascending-dose safety, pharmacokinetics and pharmacodynamics in healthy subjects. J Thromb Haemost. 2007;5 Suppl 2:P-M-664.
22.
Lopes RD, Alexander JH, Al-Khatib SM, Ansell J, Diaz R, Easton JD, et al. Apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation (ARISTOTLE) trial:design and rationale. Am Heart J. 2010;159:331–9.PubMedCrossRef
23.
Ogata K 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.PubMedCrossRef
24.
Patel M, for the ROCKET AF Study Investigators. Rivaroxaban-Once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation: rationale and design of the ROCKET AF study. Am Heart J. 2010;159:340–7.CrossRef
25.
Ruff CT, Giugliano RP, Antman EM, Crugnale SE, Bocanegra T, Mercuri M, 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. 2010;160:635–41.PubMedCrossRef
26.
27.
•• EINSTEIN Investigators, Bauersachs R, Berkowitz SD, Brenner B, et al. Oral rivaroxaban for symptomatic venous thromboembolism (and supplementary appendix). N Engl J Med. 2010;363:2499–510. This is a key trial on the use of rivaroxaban for the treatment of venous thromboembolism.PubMedCrossRef
28.
29.
NICE technology appraisal guidance 261. Rivaroxaban for the treatment of deep vein thrombosis and prevention of recurrent deep vein thrombosis and pulmonary embolism. July 2012. www.​nice.​org.​uk/​TA 261.
30.
31.
32.
•• EINSTEIN–PE Investigators, Büller HR, Prins MH, Lensin AW, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1287–97. This is a key trial on the efficacy of rivaroxaban for the treatment of symptomatic pulmonary embolism.PubMedCrossRef
33.
34.
Lassen MR, Raskob GE, Gallus A, et al. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med. 2009;36(6):594–604.CrossRef
35.
Lassen MR, Raskob GE, Gallus A, et al. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. 2010;375(9717):807–15.PubMedCrossRef
36.
Lassen MR, Gallus A, Raskob GE, et al. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement (ADVANCE-3). N Engl J Med. 2010;363(26):2487–98.PubMedCrossRef
37.
38.
39.
Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92.PubMedCrossRef
40.
Guidance in development. Stroke and systemic embolism (prevention, non-valvular atrial fibrillation) - apixaban [ID500]. www.​nice.​org.​uk.
41.
Schulman S, Kearon C, Kakkar, for the Re-COVER Study Group, et al. Dabigatran versus warfarin for the treatment of acute venous thromboembolism. N Engl Med. 2009;361:2341–52.CrossRef
42.
Agnelli G, Buller HR, Cohen A et al. Apixaban for Extended Treatment of Venous Thromboembolism. N Engl J Med. 2012 Dec 8. [Epub ahead of print].
43.
44.
45.
46.
Baglin T et al. Effects on routine coagulation screens and assessment of anticoagulant intensity in patients taking oral dabigatran or rivaroxaban: Guidence from British Committee for Standards in Haematology. Br J Haematol. 2012. doi:10.​1111/​bjh.​12052 [Epub ahead of print].
47.
• Samama MM, Guinet C. Laboratory assessments of new anticoagulants. Clin Chem Lab Med. 2011;49:761–72. This paper provides useful information on laboratory aspects of NOAC.PubMedCrossRef
48.
Samama MM, Martinoli JL, LeFlem L, et al. Assessment of laboratory assays to measure rivaroxaban-an oral, direct factor Xa inhibitor. Thromb Hemost. 2010;103(4):815–25.CrossRef
49.
Castellone DD, Van Cott EM. Laboratory monitoring of new anticoagulants. Am J Hematol. 2010;85:185–7.PubMedCrossRef
50.
• van Os GM, de Laat B, Kamphuisen PW, et al. Detection of lupus anticoagulants in the presence of rivaroxaban using Taipan snake venom time. J Thromb Haemost. 2011;9:1657–9. This small in vitro study investigates the detection of lupus anticoagulants in the presence of rivaroxaban.PubMedCrossRef
51.
Merriman E, Kaplan Z, Butler J, et al. Rivaroxaban and false positive lupus anticoagulant testing. Thromb Haemost. 2012;105:385–6.CrossRef
52.
Fareed J, Thethi I, Hoppensteadt D. Old Versus New Oral Anticoagulants: Focus on Pharmacology. Annu Rev Pharmacol Toxicol. 2012;52:79–99.PubMedCrossRef
53.
Pengo V, Crippa L, Falanga A, et al. Phase III studies on novel oral anticoagulants for stroke prevention in atrial fibrillation: a look beyond the excellent results. J Thromb Haemost. 2012;10(10):1979–87.PubMedCrossRef
54.
Buller HR. Once-daily oral rivaroxaban versus placebo in the long-term prevention of recurrent symptomatic venous thromboembolism, the Einstein-Extension Study. Late Breaking Abstracts LBA-2. 51st ASH Annual Meeting and Exposition 2009.
55.
Cohen H, Machin SJ. Antithrombotic treatment failures in antiphospholipid syndrome: the new anticoagulants? Lupus. 2010;19:486–91.PubMedCrossRef
56.
Frank Peacock W, Gearhart MM, Mills RM. Emergency Management of Bleeding Associated with Old and New Oral Anticoagulants. Clin Cardiol. 2012. doi:10.​1002/​clc.​22037 [Epub ahead of print].
57.
•• Eerenberg ES, Kamphuisen PW, Sijpken MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011;124:1573–9. This study demonstrates that prothrombin complex concentrate corrects the coagulopathy caused by rivaroxaban but not that of dabigatran.PubMedCrossRef
58.
Makris M, Joost J, Van Veen JJ, Campbell R, Tait CR, et al. Guideline on the management of bleeding in patients on antithrombotic agents. BJ Haem. 2012;160:35–46.CrossRef
59.
Turpie AGG, Kreutz R, Llau J, et al. Management consensus guidance for the use of rivaroxaban –an oral, direct factor Xa inhibitor. Thromb Haemost. 2012;108:876–86.PubMedCrossRef
60.
Spyropoulos ACD, Douketis JD. How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood. 2012;120(15):2954–62.PubMedCrossRef
61.
• Schulman S, Crowther MA. How I treat with anticoagulants in 2012: new and old anticoagulants, and when and how to switch. Blood. 2012;119(13):3016–23. This article provides authoritative advice on the clinical use of NOAC.PubMedCrossRef
62.
Douketis JD et al. Perioperative management of antithrombotic therapy: antithrombotic therapy band prevention of thrombosis 9th Edition: ACCP. Chest. 2012;141:e326Se350S.CrossRef
63.
Llau JV, Ferrandis R. New anticoagulants and regional anesthesia. Curr Opin Anaesthesiol. 2009;22:661–6.PubMedCrossRef
64.
Gogarten W, Vandermeulen E, Van Aken H, Kozek S, Llau JV, Samama CM. Regional anaesthesia and antithrombotic agents: recommendations of the European Society of Anaesthesiology. Eur J Anaesthesiol. 2010;27:999–1015.PubMedCrossRef
Metadata
Title
Use of New Oral Anticoagulants in Antiphospholipid Syndrome
Authors
Deepa Jayakody Arachchillage
Hannah Cohen
Publication date
01-06-2013
Publisher
Current Science Inc.
Published in
Current Rheumatology Reports / Issue 6/2013
Print ISSN: 1523-3774
Electronic ISSN: 1534-6307
DOI
https://doi.org/10.1007/s11926-013-0331-5

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