期刊论文详细信息
Thrombosis Journal
Practical management of patients on apixaban: a consensus guide
Simon McRae3  Alexander Gallus4  Geoffrey Donnan5  Greg Conner1  Christopher Ward2 
[1] Cardiovascular Diagnostic Services, Liverpool, NSW, Australia;Kolling Institute, University of Sydney; Royal North Shore Hospital, Sydney, NSW, Australia;Queen Elizabeth Hospital; Royal Adelaide Hospital, Woodville South, SA, Australia;Flinders Medical Center, Bedford Park, SA, Australia;Florey Institute of Neuroscience and Mental Health; The Austin Hospital, Heidelberg, VIC, Australia
关键词: Perioperative management;    Bleeding;    Novel oral anticoagulants;    Apixaban;   
Others  :  834772
DOI  :  10.1186/1477-9560-11-27
 received in 2013-09-18, accepted in 2013-11-30,  发布年份 2013
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【 摘 要 】

Background

Atrial fibrillation (AF) is a common tachyarrhythmia in Australia, with a prevalence over 10% in older patients. AF is the leading preventable cause of ischaemic stroke, and strokes due to AF have a higher mortality and morbidity. Stroke prevention is therefore a key management strategy for AF patients, in addition to rate and rhythm control. Anticoagulation with warfarin has been an enduring gold standard for stroke prevention in NVAF patients. In Australia, three novel oral anticoagulants (NOACs), apixaban, dabigatran and rivaroxaban are now approved and reimbursed for stroke prevention in patients with non-valvular AF (NVAF). International European Cardiology guidelines now recommend either a NOAC or warfarin for NVAF patients with a CHA2DS2-VASc score ≥2, unless contraindicated. Apixaban is a direct factor Xa inhibitor with a 12-hour half-life and 25% renal excretion that was found in a large trial of NVAF patients to be superior to warfarin in preventing stroke or systemic embolism. In this trial population, apixaban also resulted in less bleeding and a lower mortality rate than warfarin.

Methods

Clinical experience with apixaban outside of clinical trials has been limited, and there is currently little evidence to guide the management of bleeding or invasive procedures in patients taking apixaban. The relevant currently available animal and ex vivo human data were collected, analyzed and summarized.

Results

This multi-disciplinary consensus statement has been written to serve as a guide for healthcare practitioners prescribing apixaban in Australia, with a focus on acute and emergency management.

Conclusions

The predictable pharmacokinetics and minimal drug interactions of apixaban should allow for safe anticoagulation in the majority of patients, including temporary interruption for elective procedures. In the absence of published data, patients actively bleeding on apixaban should receive standard supportive treatment. Quantitative assays of apixaban level such as chromogenic anti-Xa assays are becoming available but their utility is unproven in this setting. Specific antidotes for novel anticoagulants, including apixaban, are in clinical development.

【 授权许可】

   
2013 Ward et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L, the RE-LY Steering Committee and Investigators: Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009, 361:1139-5.
  • [2]Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM, and the ROCKET AF Steering Committee, for the ROCKET AF Investigator: Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011, 365:883-891.
  • [3]Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, et al.: ARISTOTLE Committees and Investigators: apixaban versus warfarin in patients with atrial fibrillation. New Engl J Med 2011, 365:981-992.
  • [4]Frost C, Nepal S, Wang J, Schuster A, Barrett YC, Mosqueda-Garcia R, Reeves RA, Lacreta F: Apixaban, an oral, direct factor Xa inhibitor: single-dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects. Br J Clin Pharmacol 2013, 75(2):476-487.
  • [5]ELIQUIS® (Apixaban) Approved Product Information. Bristol-Myers Squibb Australia Pty Ltd and Pfizer Pty Ltd; 2013. http://www.bmsa.com.au/products/pages/Home.aspx webcite
  • [6]Connolly SJ, Eikelboom J, Joyner C, Diener H-C, Hart R, Golitsyn S, Flaker G, Avezum A, Hohnloser SH, Diaz R, Talajic M, Zhu J, Pais P, Budaj A, Parkhomenko A, Jansky P, Commerford P, Tan RS, Sim K-H, Lewis BS, Van Mieghem W, Lip GYH, Kim JH, Lanas-Zanetti F, Gonzalez-Hermosillo A, Dans AL, Munawar M, O’Donnell M, Lawrence J, Lewis G, et al.: Apixaban in patients with atrial fibrillation. N Engl J Med 2011, 364:806-817.
  • [7]Alexander JH, Lopes RD, James S, Kilaru R, He Y, Mohan P, Bhatt DL, Goodman S, Verheugt FW, Flather M, Huber K, Liaw D, Husted SE, Lopez-Sendon J, De Caterina R, Jansky P, Darius H, Vinereanu D, Cornel JH, Cools F, Atar D, Leiva-Pons JL, Keltai M, Ogawa H, Pais P, Parkhomenko A, Ruzyllo W, Diaz R, White H, Ruda M, et al.: Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med 2011, 365:699-708.
  • [8]Alexander JH, Becker RC, Bhatt DL, Cools F, Crea F, Dellborg M, Fox KA, Goodman SG, Harrington RA, Huber K, Husted S, Lewis BS, Lopez-Sendon J, Mohan P, Montalescot G, Ruda M, Ruzyllo W, Verheugt F, Wallentin L, APPRAISE Steering Committee and Investigators: Apixaban, an oral, direct, selective Factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome. Circulation 2009, 119:2877-2885.
  • [9]Douxfils J, Chatelain C, Chatelain B, Dogné J-M, Mullier F: Impact of apixaban on routine and specific coagulation assays: a practical laboratory guide. Thromb Haemost 2013, 110(2):283-294.
  • [10]Becker RC, Yang H, Barrett Y, Mohan P, Wang J, Wallentin LC, Alexander JH: Chromogenic laboratory assays to measure the factor Xa-inhibiting properties of apixaban—an oral, direct and selective factor Xa inhibitor. J Thromb Thrombolysis 2011, 32:183-187.
  • [11]Barrett YC, Wang Z, Frost C, Shenker A: Clinical laboratory measurement of direct factor Xa inhibitors: anti-Xa assay is preferable to prothrombin time assay. Thromb Haemost 2010, 104:1263-1271.
  • [12]Barrett YC, Wang Z, Knabb RM: A novel prothrombin time assay for assessing the anticoagulant activity of oral factor Xa inhibitors. Clin Appl Thromb Hemost 2012, 19(5):522-528.
  • [13]Upreti VV, Song Y, Wang J, Byon W, Boyd RA, Pursley JM, Lacreta F, Frost CE: Effect of famotidine on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor. Clin Pharmacol: Advances and Applications 2013, 5:59-66.
  • [14]Camm AJ, Lip GY, Caterina R, Savelieva I, Atar D, Hohnloser SH, G H, Kirchhof P, ESC Committee for Practice Guidelines (CPG): 2012 focused update of the ESC Guidelines for the management of atrial fibrillation. Eur Heart J 2012, 33:2719-2747.
  • [15]Hohnloser SH, Hijazi Z, Thomas L, Alexander JH, Amerena J, Hanna M, Keltai M, Lanas F, Lopes RD, Lopez-Sendon J, Granger CB, Wallentin L: Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J 2012, 33:2821-2830.
  • [16]Granger CB, Alexander JH, Hanna M, Wang J, Mohan P, Lawrence J, Hylek E, Ansell JE, Wallentin L, for the ARISTOTLE investigators: Events after discontinuation of randomized treatment at the end of the ARISTOTLE trial [abstract]. Eur Heart J 2012, 33(Abstract Supplement):685-686.
  • [17]Wang X, Tirucherai G, Pannacciulli , Wang J, Elsrougy A, Teslenko V, Chang M, Zhang D, Frost C: Effect of activated charcoal on the pharmacokinetics of apixaban in healthy subjects [abstract]. Clinical Pharmacol Ther 2012, 91(Suppl 1):s41.
  • [18]Lu G, DeGuzman FR, Hollenbach SJ, Karbarz MJ, Abe K, Lee G, Luan P, Hutchaleelaha A, Inagaki M, Conley PB, Phillips DR, Uma S: A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med 2013, 19(4):446-451.
  • [19]Laulicht B, Bakhru S, Lee C, Baker C, Jiang X, Mathiowitz E, Costin J, Steiner S: Small molecule antidote for anticoagulants [abstract]. Circulation 2012, 126:A11395.
  • [20]Eerenberg ES, Kamphuisen PW, Sijpkens 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, 124:1573-1579.
  • [21]Escolar G, Arellano-Rodrigo E, Reverter JC, Villalta J, Sanz V, Molina P, Diaz-Ricart M, Galan AM: Reversal of apixaban induced alterations of hemostasis by different coagulation factor concentrates: studies in vitro with circulating human blood [abstract]. Circulation 2012, 126:520-521.
  • [22]Martin AC, Le Bonniec B, Fischer AM, Marchand-Leroux C, Gaussem P, Samama CM, Godier A: Evaluation of recombinant activated factor VII, prothrombin complex concentrate, and fibrinogen concentrate to reverse apixaban in a rabbit model of bleeding and thrombosis. Int J Cardiol 2013, 168:4228-4233.
  • [23]Kaatz S, Kouides PA, Garcia DA, Spyropolous AC, Crowther M, Douketis JD, Chan AK, James A, Moll S, ORtel TL, Van Cott EM, Ansell J: Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol 2012, 87(Suppl 1):S141-S145.
  • [24]Bauer KA: Reversal of antithrombotic agents. Am J Hematol 2012, 87(Suppl 1):S119-S126.
  • [25]Fukuda T, Honda Y, Kamisato C, Morishima Y, Shibano T: Reversal of anticoagulant effects of edoxaban, an oral, direct factor Xa inhibitor, with haemostatic agents. Thromb Haemost 2012, 107:253-259.
  • [26]Marlu R, Hodaj E, Paris A, Albaladejo P, Cracowski JL, Pernod G: Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban. Thromb Haemost 2012, 108:217-224.
  • [27]Ferrandis R, Castillo J, de Andrés J, Gomar C, Gómez-Luque A, Hidalgo F, Llau JV, Sierra P, Torres LM: The perioperative management of new direct oral anticoagulants: a question without answers. Thromb Haemost 2013, 110:515-522.
  • [28]Baron TH, Kamath PS, McBane RD: Antithrombotic therapy and invasive procedures. New Engl J Med 2013, 368:1079-1080.
  • [29]Douketis JD: Pharmacologic properties of the new oral anticoagulants: a clinician-oriented review with a focus on perioperative management. Curr Pharm Des 2010, 16:3436-3441.
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