Download PDF
CC BY-NC-ND 4.0 · Thromb Haemost
DOI: 10.1055/a-2259-0662
Stroke, Systemic or Venous Thromboembolism

Comparison of Clinical Outcomes in Patients with Active Cancer Receiving Rivaroxaban or Low-Molecular-Weight Heparin: The OSCAR-UK Study

Alexander T. Cohen
1   Department of Haematological Medicine, Guy's and St Thomas' NHS Foundation Trust, King's College London, London, United Kingdom
,
Christopher Wallenhorst 
2   Institute for Epidemiology, Statistics and Informatics GmbH, Frankfurt am Main, Germany
,
Marcella Rivera
3   Bayer AG, Berlin, Germany at the time of study conduct, currently affiliated to Janssen Research and Development, Barcelona, Spain
,
Cihan Ay
4   Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
,
Bernhard Schaefer
5   Bayer AG, Berlin, Germany
,
Khaled Abdelgawwad
5   Bayer AG, Berlin, Germany
,
George Psaroudakis
5   Bayer AG, Berlin, Germany
,
Gunnar Brobert
5   Bayer AG, Berlin, Germany
,
Anders Ekbom
6   Unit of Clinical Epidemiology, Department of Medicine, Karolinska Institute, Stockholm, Sweden
,
Agnes Y. Y. Lee
7   Division of Hematology, University of British Columbia and BC Cancer, Vancouver, Canada
,
Alok A. Khorana 
8   Cleveland Clinic and Case Comprehensive Cancer Center, Cleveland, Ohio, United States
,
Cecilia Becattini
9   Department of Internal and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy
,
Marc Carrier
10   Department of Medicine, Ottawa Hospital Research Institute at the University of Ottawa, Ottawa, Canada
,
Craig I. Coleman 
11   Department of Pharmacy Practice, School of Pharmacy, University of Connecticut, Storrs, Connecticut, United States
,
Carlos Martinez 
2   Institute for Epidemiology, Statistics and Informatics GmbH, Frankfurt am Main, Germany
› Author Affiliations Funding The study was funded by Bayer.
› Further Information
   Permissions and Reprints


Abstract

Background In most patients with cancer-associated venous thromboembolism (CT), essentially those not at high risk of bleeding, guidelines recommend treatment with direct oral anticoagulants as an alternative to low-molecular-weight heparins (LMWHs). Population-based studies comparing these therapies are scarce.

Objectives To compare the risk of venous thromboembolism (VTE) recurrences, significant bleeding, and all-cause mortality in patients with CT receiving rivaroxaban or LMWHs.

Patients/Methods Using UK Clinical Practice Research Datalink data from 2013 to 2020, we generated a cohort of patients with first CT treated initially with either rivaroxaban or LMWH. Patients were observed 12 months for VTE recurrences, significant bleeds (major bleeds or clinically relevant nonmajor bleeding requiring hospitalization), and all-cause mortality. Overlap weighted sub-distribution hazard ratios (SHRs) compared rivaroxaban with LMWH in an intention-to-treat analysis.

Results The cohort consisted of 2,259 patients with first CT, 314 receiving rivaroxaban, and 1,945 LMWH, mean age 72.4 and 66.9 years, respectively. In the 12-month observational period, 184 person-years following rivaroxaban and 1,057 following LMWH, 10 and 66 incident recurrent VTE events, 20 and 102 significant bleeds, and 10 and 133 deaths were observed in rivaroxaban and LMWH users, respectively. The weighted SHR at 12 months for VTE recurrences in rivaroxaban compared with LMWH were 0.80 (0.37–1.73); for significant bleeds 1.01 (0.57–1.81); and for all-cause mortality 0.49 (0.23–1.06).

Conclusion Patients with CT, not at high risk of bleeding, treated with either rivaroxaban or LMWH have comparable effectiveness and safety outcomes. This supports the recommendation that rivaroxaban is a reasonable alternative to LMWH for the treatment of CT.

Keywords

venous thromboembolism - anticoagulants - cancer

Note

Trial registration number: NCT05112666


Supplementary Material



Publication History

Received: 07 July 2023

Accepted: 08 December 2023

Accepted Manuscript online:
01 February 2024

Article published online:
08 April 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Prandoni P, Lensing AWA, Piccioli A. et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002; 100 (10) 3484-3488
    Google Scholar
  • 2 Cohen AT, Katholing A, Rietbrock S, Bamber L, Martinez C. Epidemiology of first and recurrent venous thromboembolism in patients with active cancer. A population-based cohort study. Thromb Haemost 2017; 117 (01) 57-65
    Google Scholar
  • 3 Weitz JI, Haas S, Ageno W. et al; GARFIELD-VTE investigators. Cancer associated thrombosis in everyday practice: perspectives from GARFIELD-VTE. J Thromb Thrombolysis 2020; 50 (02) 267-277
    Google Scholar
  • 4 Lyman GH, Carrier M, Ay C. et al. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Adv 2021; 5 (04) 927-974
    Google Scholar
  • 5 Cuker A, Tseng EK, Nieuwlaat R. et al. American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19. Blood Adv 2021; 5 (03) 872-888
    Google Scholar
  • 6 Khorana AA, Noble S, Lee AYY. et al. Role of direct oral anticoagulants in the treatment of cancer-associated venous thromboembolism: guidance from the SSC of the ISTH. J Thromb Haemost 2018; 16 (09) 1891-1894
    Google Scholar
  • 7 Giustozzi M, Agnelli G, Del Toro-Cervera J. et al. Direct oral anticoagulants for the treatment of acute venous thromboembolism associated with cancer: a systematic review and meta-analysis. Thromb Haemost 2020; 120 (07) 1128-1136
    Google Scholar
  • 8 Mahé I, Plaisance L, Chapelle C. et al. Long-term treatment of cancer-associated thrombosis (CAT) beyond 6 months in the medical practice: USCAT, a 432-patient retrospective non-interventional study. Cancers (Basel) 2020; 12 (08) 12
    Google Scholar
  • 9 Sakamoto J, Yamashita Y, Morimoto T. et al; COMMAND VTE Registry Investigators. Cancer-associated venous thromboembolism in the real world - From the COMMAND VTE registry. Circ J 2019; 83 (11) 2271-2281
    Google Scholar
  • 10 Coleman C, Caroti KS, Abdelgawwad K. et al. Patient characteristics and temporal changes in anticoagulation treatment patterns in patients diagnosed with cancer-associated thrombosis: an Oscar-US Analysis. Blood 2021; 138 (01) 2132
    Google Scholar
  • 11 Martinez C, Cohen AT, Bamber L, Rietbrock S. Epidemiology of first and recurrent venous thromboembolism: a population-based cohort study in patients without active cancer. Thromb Haemost 2014; 112 (02) 255-263
    Google Scholar
  • 12 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
    Google Scholar
  • 13 Bayer AG. A study to gather information about rivaroxaban in patients in the United Kingdom who have cancer and thrombosis (OSCAR-UK). 2021 . Accessed February 9, 2024 at: https://clinicaltrials.gov/ct2/show/NCT05112666
    Google Scholar
  • 14 Martinez C, Katholing A, Wallenhorst C, Cohen AT. Prediction of significant bleeding during vitamin K antagonist treatment for venous thromboembolism in outpatients. Br J Haematol 2020; 189 (03) 524-533
    Google Scholar
  • 15 Li F, Thomas LE, Li F. Addressing extreme propensity scores via the overlap weights. Am J Epidemiol 2019; 188 (01) 250-257
    Google Scholar
  • 16 Thomas LE, Li F, Pencina MJ. Overlap weighting: a propensity score method that mimics attributes of a randomized clinical trial. JAMA 2020; 323 (23) 2417-2418
    Google Scholar
  • 17 Schoenfeld D. Partial residuals for the proportional hazards model. Biometrika 1982; 69: 51-55
    Google Scholar
  • 18 Coleman CI, Caroti KS, Abdelgawwad K. et al. Effectiveness and safety of rivaroxban and low molecular-weight heparin in cancer-assocaited venous thromboembolism. JACC Cardiooncol 2023; 5 (02) 189-200
    Google Scholar
  • 19 Cominacini M, Suardi S, Ferrari G. et al. DOAC in the treatment of cancer-associated venous thromboembolism: a retrospective cohort study beyond the guidelines. J Cancer Res Clin Oncol 2023; 149 (09) 5773-5779
    Google Scholar
  • 20 Michalopoulou H, Polyzos D, Thomopoulos C. et al. Net clinical benefit of DOACs vs. usual anticoagulation treatment in venous thromboembolism and active cancer: systematic review and meta-analysis. J Thromb Thrombolysis 2023; 55 (01) 92-101
    Google Scholar
  • 21 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
    Google Scholar
  • 22 Raskob GE, van Es N, Verhamme P. et al; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 2018; 378 (07) 615-624
    Google Scholar
  • 23 Young AM, Marshall A, Thirlwall J. et al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol 2018; 36 (20) 2017-2023
    Google Scholar
  • 24 Bayer AG. A study to gather information about rivaroxaban in patients in Sweden with cancer who also have thrombosis (OSCAR-SE). Accessed December 17, 2021 at: https://clinicaltrials.gov/ct2/show/NCT05150938?term=oscar-se&draw=2&rank=1
    Google Scholar