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Published in: Advances in Therapy 3/2017

Open Access 01-03-2017 | Review

Edoxaban in Atrial Fibrillation and Venous Thromboembolism—Ten Key Questions and Answers: A Practical Guide

Authors: Raffaele De Caterina, Walter Ageno, Giuseppe Boriani, Paolo Colonna, Angelo Ghirarduzzi, Giuseppe Patti, Roberta Rossini, Andrea Rubboli, Piercarla Schinco, Giancarlo Agnelli

Published in: Advances in Therapy | Issue 3/2017

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Abstract

Edoxaban is the fourth non-vitamin K antagonist oral anticoagulant now available for clinical use in the prevention of stroke/systemic embolism in atrial fibrillation (AF) and in the treatment of venous thromboembolism (VTE), after the completion of large-scale randomized comparative clinical trials with the vitamin K antagonist warfarin. Edoxaban has some peculiar pharmacological properties and outcome data. Here a group of experts in AF and VTE answers a set of questions on its practical use, trying to define the profile of patients that would be most appropriate for its use.
Literature
1.
go back to reference Stacy ZA, Call WB, Hartmann AP, et al. Edoxaban: a comprehensive review of the pharmacology and clinical data for the management of atrial fibrillation and venous thromboembolism. Cardiol Ther. 2016;5:1–18.CrossRefPubMedPubMedCentral Stacy ZA, Call WB, Hartmann AP, et al. Edoxaban: a comprehensive review of the pharmacology and clinical data for the management of atrial fibrillation and venous thromboembolism. Cardiol Ther. 2016;5:1–18.CrossRefPubMedPubMedCentral
3.
go back to reference Steffel J, Giugliano RP, Braunwald E, et al. Edoxaban vs. warfarin in patients with atrial fibrillation on amiodarone: a subgroup analysis of the ENGAGE AF-TIMI 48 trial. Eur Heart J. 2015;36:2239–45.CrossRefPubMed Steffel J, Giugliano RP, Braunwald E, et al. Edoxaban vs. warfarin in patients with atrial fibrillation on amiodarone: a subgroup analysis of the ENGAGE AF-TIMI 48 trial. Eur Heart J. 2015;36:2239–45.CrossRefPubMed
4.
go back to reference Ruff CT, Giugliano RP, Braunwald E, et al. Association between edoxaban dose, concentration, anti-factor Xa activity, and outcomes: an analysis of data from the randomised, double-blind ENGAGE AF-TIMI 48 trial. Lancet. 2015;385:2288–95.CrossRefPubMed Ruff CT, Giugliano RP, Braunwald E, et al. Association between edoxaban dose, concentration, anti-factor Xa activity, and outcomes: an analysis of data from the randomised, double-blind ENGAGE AF-TIMI 48 trial. Lancet. 2015;385:2288–95.CrossRefPubMed
5.
go back to reference Rognoni C, Marchetti M, Quaglini S, et al. Edoxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation: a cost-effectiveness analysis. J Thromb Thrombolysis. 2015;39:149–54.CrossRefPubMed Rognoni C, Marchetti M, Quaglini S, et al. Edoxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation: a cost-effectiveness analysis. J Thromb Thrombolysis. 2015;39:149–54.CrossRefPubMed
6.
go back to reference Connolly SJ, Milling TJ Jr, Eikelboom JW, et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med. 2016;375:1131–41.CrossRefPubMed Connolly SJ, Milling TJ Jr, Eikelboom JW, et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med. 2016;375:1131–41.CrossRefPubMed
7.
go back to reference Zahir H, Brown KS, Vandell AG, et al. Edoxaban effects on bleeding following punch biopsy and reversal by a 4-factor prothrombin complex concentrate. Circulation. 2015;131:82–90.CrossRefPubMed Zahir H, Brown KS, Vandell AG, et al. Edoxaban effects on bleeding following punch biopsy and reversal by a 4-factor prothrombin complex concentrate. Circulation. 2015;131:82–90.CrossRefPubMed
8.
go back to reference Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369:2093–104.CrossRefPubMed Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369:2093–104.CrossRefPubMed
9.
go back to reference Weitz JI, Connolly SJ, Patel I, et al. Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation. Thromb Haemost. 2010;104:633–41.CrossRefPubMed Weitz JI, Connolly SJ, Patel I, et al. Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation. Thromb Haemost. 2010;104:633–41.CrossRefPubMed
10.
go back to reference Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.CrossRefPubMed Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.CrossRefPubMed
11.
go back to reference Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.CrossRefPubMed Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.CrossRefPubMed
12.
go back to reference Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92.CrossRefPubMed Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92.CrossRefPubMed
13.
go back to reference Buller HR, Decousus H, Grosso MA, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369:1406–15.CrossRefPubMed Buller HR, Decousus H, Grosso MA, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369:1406–15.CrossRefPubMed
14.
go back to reference Bae JP, Dobesh PP, Klepser DG, et al. Adherence and dosing frequency of common medications for cardiovascular patients. Am J Manag Care. 2012;18:139–46.PubMed Bae JP, Dobesh PP, Klepser DG, et al. Adherence and dosing frequency of common medications for cardiovascular patients. Am J Manag Care. 2012;18:139–46.PubMed
15.
go back to reference Laliberte F, Nelson WW, Lefebvre P, et al. Impact of daily dosing frequency on adherence to chronic medications among nonvalvular atrial fibrillation patients. Adv Ther. 2012;29:675–90.CrossRefPubMed Laliberte F, Nelson WW, Lefebvre P, et al. Impact of daily dosing frequency on adherence to chronic medications among nonvalvular atrial fibrillation patients. Adv Ther. 2012;29:675–90.CrossRefPubMed
16.
go back to reference Renda G, De Caterina R. The new oral anticoagulants in atrial fibrillation: once daily or twice daily? Vascul Pharmacol. 2013;59:53–62.CrossRefPubMed Renda G, De Caterina R. The new oral anticoagulants in atrial fibrillation: once daily or twice daily? Vascul Pharmacol. 2013;59:53–62.CrossRefPubMed
17.
go back to reference Alberts MJ, Peacock WF, Fields LE, et al. Association between once- and twice-daily direct oral anticoagulant adherence in nonvalvular atrial fibrillation patients and rates of ischemic stroke. Int J Cardiol. 2016;215:11–3.CrossRefPubMed Alberts MJ, Peacock WF, Fields LE, et al. Association between once- and twice-daily direct oral anticoagulant adherence in nonvalvular atrial fibrillation patients and rates of ischemic stroke. Int J Cardiol. 2016;215:11–3.CrossRefPubMed
18.
go back to reference Bathala MS, Masumoto H, Oguma T, et al. Pharmacokinetics, biotransformation, and mass balance of edoxaban, a selective, direct factor Xa inhibitor, in humans. Drug Metab Dispos. 2012;40:2250–5.CrossRefPubMed Bathala MS, Masumoto H, Oguma T, et al. Pharmacokinetics, biotransformation, and mass balance of edoxaban, a selective, direct factor Xa inhibitor, in humans. Drug Metab Dispos. 2012;40:2250–5.CrossRefPubMed
20.
go back to reference Mueck W, Kubitza D, Becka M. Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects. Br J Clin Pharmacol. 2013;76:455–66.CrossRefPubMedPubMedCentral Mueck W, Kubitza D, Becka M. Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects. Br J Clin Pharmacol. 2013;76:455–66.CrossRefPubMedPubMedCentral
21.
go back to reference Wang L, Zhang D, Raghavan N, 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 Wang L, Zhang D, Raghavan N, 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
22.
go back to reference Heidbuchel H, Verhamme P, Alings M, 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. 2015;17:1467–507.CrossRefPubMed Heidbuchel H, Verhamme P, Alings M, 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. 2015;17:1467–507.CrossRefPubMed
23.
go back to reference Dans AL, Connolly SJ, Wallentin L, et al. Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Circulation. 2013;127:634–40.CrossRefPubMed Dans AL, Connolly SJ, Wallentin L, et al. Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Circulation. 2013;127:634–40.CrossRefPubMed
24.
go back to reference Alexander JH, Lopes RD, Thomas L, et al. Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J. 2014;35:224–32.CrossRefPubMed Alexander JH, Lopes RD, Thomas L, et al. Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J. 2014;35:224–32.CrossRefPubMed
25.
go back to reference Mahaffey KW, Stevens SR, White HD, et al. Ischaemic cardiac outcomes in patients with atrial fibrillation treated with vitamin K antagonism or factor Xa inhibition: results from the ROCKET AF trial. Eur Heart J. 2014;35:233–41.CrossRefPubMed Mahaffey KW, Stevens SR, White HD, et al. Ischaemic cardiac outcomes in patients with atrial fibrillation treated with vitamin K antagonism or factor Xa inhibition: results from the ROCKET AF trial. Eur Heart J. 2014;35:233–41.CrossRefPubMed
26.
go back to reference Lamberts M, Gislason GH, Lip GY, et al. Antiplatelet therapy for stable coronary artery disease in atrial fibrillation patients taking an oral anticoagulant: a nationwide cohort study. Circulation. 2014;129:1577–85.CrossRefPubMed Lamberts M, Gislason GH, Lip GY, et al. Antiplatelet therapy for stable coronary artery disease in atrial fibrillation patients taking an oral anticoagulant: a nationwide cohort study. Circulation. 2014;129:1577–85.CrossRefPubMed
27.
go back to reference Xu H, Ruff CT, Giugliano RP, et al. Concomitant use of single antiplatelet therapy with edoxaban or warfarin in patients with atrial fibrillation: analysis from the ENGAGE AF-TIMI48 Trial. J Am Heart Assoc. 2016;5:e002587.CrossRefPubMedPubMedCentral Xu H, Ruff CT, Giugliano RP, et al. Concomitant use of single antiplatelet therapy with edoxaban or warfarin in patients with atrial fibrillation: analysis from the ENGAGE AF-TIMI48 Trial. J Am Heart Assoc. 2016;5:e002587.CrossRefPubMedPubMedCentral
28.
go back to reference Boriani G, Laroche C, Diemberger I, et al. Asymptomatic atrial fibrillation: clinical correlates, management, and outcomes in the EORP-AF Pilot General Registry. Am J Med. 2015;128:509 e2–18 e2.CrossRef Boriani G, Laroche C, Diemberger I, et al. Asymptomatic atrial fibrillation: clinical correlates, management, and outcomes in the EORP-AF Pilot General Registry. Am J Med. 2015;128:509 e2–18 e2.CrossRef
29.
go back to reference Boriani G, Savelieva I, Dan GA, et al. Chronic kidney disease in patients with cardiac rhythm disturbances or implantable electrical devices: clinical significance and implications for decision making-a position paper of the European Heart Rhythm Association endorsed by the Heart Rhythm Society and the Asia Pacific Heart Rhythm Society. Europace. 2015;17:1169–96.CrossRefPubMed Boriani G, Savelieva I, Dan GA, et al. Chronic kidney disease in patients with cardiac rhythm disturbances or implantable electrical devices: clinical significance and implications for decision making-a position paper of the European Heart Rhythm Association endorsed by the Heart Rhythm Society and the Asia Pacific Heart Rhythm Society. Europace. 2015;17:1169–96.CrossRefPubMed
30.
go back to reference Nielsen PB, Lane DA, Rasmussen LH, et al. Renal function and non-vitamin K oral anticoagulants in comparison with warfarin on safety and efficacy outcomes in atrial fibrillation patients: a systemic review and meta-regression analysis. Clin Res Cardiol. 2015;104:418–29.CrossRefPubMed Nielsen PB, Lane DA, Rasmussen LH, et al. Renal function and non-vitamin K oral anticoagulants in comparison with warfarin on safety and efficacy outcomes in atrial fibrillation patients: a systemic review and meta-regression analysis. Clin Res Cardiol. 2015;104:418–29.CrossRefPubMed
31.
go back to reference Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285:2370–5.CrossRefPubMed Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285:2370–5.CrossRefPubMed
32.
go back to reference Kato ET, Giugliano RP, Ruff CT, et al. Efficacy and safety of edoxaban in elderly patients with atrial fibrillation in the ENGAGE AF-TIMI 48 Trial. J Am Heart Assoc. 2016;5:e003432.CrossRefPubMedPubMedCentral Kato ET, Giugliano RP, Ruff CT, et al. Efficacy and safety of edoxaban in elderly patients with atrial fibrillation in the ENGAGE AF-TIMI 48 Trial. J Am Heart Assoc. 2016;5:e003432.CrossRefPubMedPubMedCentral
33.
go back to reference Gage BF, Birman-Deych E, Kerzner R, et al. Incidence of intracranial hemorrhage in patients with atrial fibrillation who are prone to fall. Am J Med. 2005;118:612–7.CrossRefPubMed Gage BF, Birman-Deych E, Kerzner R, et al. Incidence of intracranial hemorrhage in patients with atrial fibrillation who are prone to fall. Am J Med. 2005;118:612–7.CrossRefPubMed
34.
go back to reference Gage BF, Yan Y, Milligan PE, et al. Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J. 2006;151:713–9.CrossRefPubMed Gage BF, Yan Y, Milligan PE, et al. Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J. 2006;151:713–9.CrossRefPubMed
35.
go back to reference Man-Son-Hing M, Nichol G, Lau A, et al. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med. 1999;159:677–85.CrossRefPubMed Man-Son-Hing M, Nichol G, Lau A, et al. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med. 1999;159:677–85.CrossRefPubMed
37.
go back to reference Dries DL, Exner DV, Gersh BJ, et al. Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials. Studies of Left Ventricular Dysfunction. J Am Coll Cardiol. 1998;32:695–703.CrossRefPubMed Dries DL, Exner DV, Gersh BJ, et al. Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials. Studies of Left Ventricular Dysfunction. J Am Coll Cardiol. 1998;32:695–703.CrossRefPubMed
38.
go back to reference Magnani G, Giugliano RP, Ruff CT, et al. Efficacy and safety of edoxaban compared with warfarin in patients with atrial fibrillation and heart failure: insights from ENGAGE AF-TIMI 48. Eur J Heart Fail. 2016;18:1153–61. Magnani G, Giugliano RP, Ruff CT, et al. Efficacy and safety of edoxaban compared with warfarin in patients with atrial fibrillation and heart failure: insights from ENGAGE AF-TIMI 48. Eur J Heart Fail. 2016;18:1153–61.
39.
go back to reference Bohula EA, Giugliano RP, Ruff CT, et al. Impact of renal function on outcomes with edoxaban in the ENGAGE AF-TIMI 48 Trial. Circulation. 2016;134:24–36.CrossRefPubMed Bohula EA, Giugliano RP, Ruff CT, et al. Impact of renal function on outcomes with edoxaban in the ENGAGE AF-TIMI 48 Trial. Circulation. 2016;134:24–36.CrossRefPubMed
41.
42.
go back to reference Heit JA, Lahr BD, Petterson TM, et al. Heparin and warfarin anticoagulation intensity as predictors of recurrence after deep vein thrombosis or pulmonary embolism: a population-based cohort study. Blood. 2011;118:4992–9.CrossRefPubMedPubMedCentral Heit JA, Lahr BD, Petterson TM, et al. Heparin and warfarin anticoagulation intensity as predictors of recurrence after deep vein thrombosis or pulmonary embolism: a population-based cohort study. Blood. 2011;118:4992–9.CrossRefPubMedPubMedCentral
43.
go back to reference Murin S, Romano PS, White RH. Comparison of outcomes after hospitalization for deep venous thrombosis or pulmonary embolism. Thromb Haemost. 2002;88:407–14.PubMed Murin S, Romano PS, White RH. Comparison of outcomes after hospitalization for deep venous thrombosis or pulmonary embolism. Thromb Haemost. 2002;88:407–14.PubMed
44.
go back to reference 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:e419S–94S.CrossRefPubMedPubMedCentral 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:e419S–94S.CrossRefPubMedPubMedCentral
45.
go back to reference Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149:315–52.CrossRefPubMed Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149:315–52.CrossRefPubMed
46.
go back to reference Raskob G, Ageno W, Cohen AT, et al. Extended duration of anticoagulation with edoxaban in patients with venous thromboembolism: a post hoc analysis of the Hokusai-VTE study. Lancet Haematol. 2016;3:e228–36.CrossRefPubMed Raskob G, Ageno W, Cohen AT, et al. Extended duration of anticoagulation with edoxaban in patients with venous thromboembolism: a post hoc analysis of the Hokusai-VTE study. Lancet Haematol. 2016;3:e228–36.CrossRefPubMed
Metadata
Title
Edoxaban in Atrial Fibrillation and Venous Thromboembolism—Ten Key Questions and Answers: A Practical Guide
Authors
Raffaele De Caterina
Walter Ageno
Giuseppe Boriani
Paolo Colonna
Angelo Ghirarduzzi
Giuseppe Patti
Roberta Rossini
Andrea Rubboli
Piercarla Schinco
Giancarlo Agnelli
Publication date
01-03-2017
Publisher
Springer Healthcare
Published in
Advances in Therapy / Issue 3/2017
Print ISSN: 0741-238X
Electronic ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-017-0488-9

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