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CC BY 4.0 · TH Open 2021; 05(02): e143-e151
DOI: 10.1055/s-0041-1728675
Original Article

Venous Thromboembolism Therapy with Apixaban in Daily Care Patients: Results from the Dresden NOAC Registry

Jan Beyer-Westendorf
1   Thrombosis Research Unit, Division Hematology, Department of Medicine I, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
2   Kings Thrombosis Service, Department of Hematology, Kings College, London, United Kingdom
,
Sandra Marten
1   Thrombosis Research Unit, Division Hematology, Department of Medicine I, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Luise Tittl
1   Thrombosis Research Unit, Division Hematology, Department of Medicine I, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Christiane Naue
1   Thrombosis Research Unit, Division Hematology, Department of Medicine I, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Martin Bornhäuser
1   Thrombosis Research Unit, Division Hematology, Department of Medicine I, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
› Author Affiliations Funding The DRESDEN NOAC REGISTRY is supported by the Gesellschaft für Technologie- und Wissenstransfer der Technischen Universität Dresden (GWT-TUD GmbH), Germany (sponsor), by research funds of the University Hospital “Carl Gustav Carus,” Dresden, and by the grants from Bayer HealthCare, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer. All authors declare that these companies and institutions had no influence on the study design, conduct of the study, data collection, statistical analysis, or preparation of the manuscript.
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Abstract

The effectiveness and safety of venous thromboembolism (VTE) treatment with apixaban, demonstrated in phase III trials, need to be confirmed in daily care.

Using data from the prospective, noninterventional cross-indication Dresden NOAC Registry we evaluated rates of VTE recurrence and bleeding complications during apixaban treatment of VTE patients. For this analysis, we only included patients with acute VTE who started apixaban within 14 days after diagnosis and who were enrolled within these 14 days. Patient characteristics, treatment persistence, and clinical outcomes were assessed.

Between August 1st, 2014 and October 31, 2018, 352 patients with apixaban treatment for acute VTE were enrolled. During treatment (median exposure 13.7 ± 9.8 months; median follow-up 21.7 ± 6.1 months) rates of recurrent VTE and International Society on Thrombosis and Haemostasis major bleeding were 1.3/100 pt.years (95% confidence interval or CI 0.4–3.0) and 1.5/100 pt.years (0.6–3.3), respectively. At 6 months. 68.6% of patients were still taking apixaban, 23.9% had a scheduled end of treatment, 6.3% were switched to other anticoagulants, and the remaining 2.3% had unplanned complete discontinuation of anticoagulation.

Of the 188 patients stopping apixaban, 12 (6.4%) experienced a recurrent VTE (six pulmonary embolisms ± deep vein thrombosis, six deep vein thrombosis; mean time between stopping anticoagulation and VTE recurrence 5.2 ± 4.1 months [range 14–417 days]).

Our findings suggest that, in daily care, apixaban demonstrated high effectiveness, safety, and persistence in the treatment of acute VTE with low rates of unplanned discontinuation.

Keywords

anticoagulation - bleeding - persistence - apixaban - venous thromboembolism

Ethics

The study protocol of the DRESDEN NOAC REGISTRY was approved by the local ethics committee at the Technical University Dresden (AZ EK 349092011) and registered at ClinicalTrials.gov (NCT01588119). The study complies with the principles and requirements of the Declaration of Helsinki. All patients provided written informed consent, including a data protection waiver, before enrolment.


Authors' Contributions

J.B.-W. has designed this analysis and has written the first draft of the manuscript. L.T., S.M., and C.N. have collected the data. L.T. has performed the statistical analyses and drafted the figures. All authors have provided significant contributions to the written presentation, have critically reviewed and approved the final version of the manuscript.


Supplementary Material



Publication History

Received: 23 April 2020

Accepted: 23 February 2021

Article published online:
04 May 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 van Es N, Coppens M, Schulman S, Middeldorp S, Büller HR. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood 2014; 124 (12) 1968-1975
    CrossrefPubMedGoogle Scholar
  • 2 Kearon C, Akl EA, Ornelas J. et al. Antithrombotic therapy for VTE disease: Chest guideline and expert panel report. Chest 2016; 149 (02) 315-352
    CrossrefPubMedGoogle Scholar
  • 3 Konstantinides SV, Meyer G, Becattini C. et al; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020; 41 (04) 543-603
    CrossrefPubMedGoogle Scholar
  • 4 Agnelli G, Buller HR, Cohen A. et al; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369 (09) 799-808
    CrossrefPubMedGoogle Scholar
  • 5 Agnelli G, Buller HR, Cohen A. et al; AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 2013; 368 (08) 699-708
    CrossrefPubMedGoogle Scholar
  • 6 Agnelli G, Becattini C, Meyer G. et al; Caravaggio Investigators. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med 2020; 382 (17) 1599-1607
    CrossrefPubMedGoogle Scholar
  • 7 Beyer-Westendorf J, Lensing AW, Arya R. et al. Choosing wisely: the impact of patient selection on efficacy and safety outcomes in the EINSTEIN-DVT/PE and AMPLIFY trials. Thromb Res 2017; 149: 29-37
    CrossrefPubMedGoogle Scholar
  • 8 Beyer-Westendorf J, Förster K, Pannach S. et al. Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry. Blood 2014; 124 (06) 955-962
    CrossrefPubMedGoogle Scholar
  • 9 Schellong SM, Gerlach H, Hach-Wunderle V. et al. Diagnosis of deep-vein thrombosis: adherence to guidelines and outcomes in real-world health care. Thromb Haemost 2009; 102 (06) 1234-1240
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
    CrossrefPubMedGoogle Scholar
  • 11 Helmert S, Marten S, Mizera H. et al. Effectiveness and safety of apixaban therapy in daily-care patients with atrial fibrillation: results from the Dresden NOAC Registry. J Thromb Thrombolysis 2017; 44 (02) 169-178
    CrossrefPubMedGoogle Scholar
  • 12 Kearon C, Ageno W, Cannegieter SC, Cosmi B, Geersing GJ, Kyrle PA. Subcommittees on Control of Anticoagulation, and Predictive and Diagnostic Variables in Thrombotic Disease. Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH. J Thromb Haemost 2016; 14 (07) 1480-1483
    CrossrefPubMedGoogle Scholar
  • 13 Lutsey PL, Walker RF, MacLehose RF, Alonso A, Adam TJ, Zakai NA. Direct oral anticoagulants and warfarin for venous thromboembolism treatment: trends from 2012 to 2017. Res Pract Thromb Haemost 2019; 3 (04) 668-673
    CrossrefPubMedGoogle Scholar
  • 14 Dawwas GK, Brown J, Dietrich E, Park H. Effectiveness and safety of apixaban versus rivaroxaban for prevention of recurrent venous thromboembolism and adverse bleeding events in patients with venous thromboembolism: a retrospective population-based cohort analysis. Lancet Haematol 2019; 6 (01) e20-e28
    CrossrefPubMedGoogle Scholar
  • 15 Dawwas GK, Smith SM, Dietrich E, Lo-Ciganic WH, Park H. Comparative effectiveness and safety of apixaban versus warfarin in patients with venous thromboembolism. Am J Health Syst Pharm 2020; 77 (03) 188-195
    CrossrefPubMedGoogle Scholar
  • 16 Haastrup SB, Hellfritzsch M, Rasmussen L, Pottegård A, Grove EL. Use of non-vitamin K antagonist oral anticoagulants 2008-2016: a Danish Nationwide Cohort Study. Basic Clin Pharmacol Toxicol 2018; 123 (04) 452-463
    CrossrefPubMedGoogle Scholar
  • 17 Weycker D, Li X, Wygant GD. et al. Effectiveness and safety of apixaban versus warfarin as outpatient treatment of venous thromboembolism in U.S. Clinical Practice. Thromb Haemost 2018; 118 (11) 1951-1961
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Bott-Kitslaar DM, McBane RD, Casanegra AI. et al. Apixaban and rivaroxaban in patients with acute venous thromboembolism. Mayo Clin Proc 2019; 94 (07) 1242-1252
    CrossrefPubMedGoogle Scholar
  • 19 Beyer-Westendorf J, Förster K, Ebertz F. et al. Drug persistence with rivaroxaban therapy in atrial fibrillation patients-results from the Dresden non-interventional oral anticoagulation registry. Europace 2015; 17 (04) 530-538
    CrossrefPubMedGoogle Scholar
  • 20 Keller L, Marten S, Hecker J, Sahin K, Tittl L, Beyer-Westendorf J. Venous thromboembolism therapy with rivaroxaban in daily-care patients: results from the Dresden NOAC registry. Int J Cardiol 2018; 257: 276-282
    CrossrefPubMedGoogle Scholar
  • 21 Willey VJ, Bullano MF, Hauch O. et al. Management patterns and outcomes of patients with venous thromboembolism in the usual community practice setting. Clin Ther 2004; 26 (07) 1149-1159
    CrossrefPubMedGoogle Scholar
  • 22 Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann Intern Med 2003; 139 (11) 893-900
    Google Scholar
  • 23 Sindet-Pedersen C, Staerk L, Pallisgaard JL. et al. Safety and effectiveness of rivaroxaban and apixaban in patients with venous thromboembolism: a nationwide study. Eur Heart J Cardiovasc Pharmacother 2018; 4 (04) 220-227
    CrossrefPubMedGoogle Scholar
  • 24 Ageno W, Mantovani LG, Haas S. et al. XALIA: rationale and design of a non-interventional study of rivaroxaban compared with standard therapy for initial and long-term anticoagulation in deep vein thrombosis. Thromb J 2014; 12: 16
    CrossrefPubMedGoogle Scholar
  • 25 Ageno W, Mantovani LG, Haas S. et al. Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study. Lancet Haematol 2016; 3 (01) e12-e21
    Google Scholar