CC BY 4.0 · TH Open 2023; 07(03): e206-e216
DOI: 10.1055/s-0043-1770783
Original Article

Rivaroxaban versus Apixaban for Treatment of Cancer-Associated Venous Thromboembolism in Patients at Lower Risk of Bleeding

Kimberly Snow Caroti
1   Department of Pharmacy Practice, School of Pharmacy, University of Connecticut, Storrs, Connecticut, United States
2   Evidence-Based Practice Center, Hartford Hospital, Hartford, Connecticut, United States
Cecilia Becattini
3   Department of Internal and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy
Marc Carrier
4   Department of Medicine, Ottawa Hospital Research Institute at the University of Ottawa, Ottawa, Canada
Alexander T. Cohen
5   Department of Haematological Medicine, Guy's and St Thomas' NHS Foundation Trust, King's College London, London, United Kingdom
Anders Ekbom
6   Unit of Clinical Epidemiology, Department of Medicine, Karolinska Institute, Stockholm, Sweden
Alok A. Khorana
7   Cleveland Clinic and Case Comprehensive Cancer Center, Cleveland, Ohio, United States
Agnes Y.Y. Lee
8   Department of Medicine, University of British Columbia and BC Cancer, Vancouver, Canada
Christopher Brescia
9   Freshtech IT, LLC, East Hartford, Connecticut, United States
Khaled Abdelgawwad
10   Pharmacoepidemiology Group, Bayer AG, Berlin, Germany
George Psaroudakis
10   Pharmacoepidemiology Group, Bayer AG, Berlin, Germany
Marcela Riveraa
10   Pharmacoepidemiology Group, Bayer AG, Berlin, Germany
Bernhard Schaeferb
10   Pharmacoepidemiology Group, Bayer AG, Berlin, Germany
Gunnar Brobertb
10   Pharmacoepidemiology Group, Bayer AG, Berlin, Germany
1   Department of Pharmacy Practice, School of Pharmacy, University of Connecticut, Storrs, Connecticut, United States
2   Evidence-Based Practice Center, Hartford Hospital, Hartford, Connecticut, United States
› Author Affiliations


This retrospective study, utilizing U.S. electronic health record (EHR) data from January 2013 to December 2020, sought to assess whether rivaroxaban and apixaban had similar effectiveness and safety in the treatment of cancer-associated venous thromboembolism (VTE) in patients with a cancer type not associated with a high risk of bleeding. We included adults diagnosed with active cancer, excluding esophageal, gastric, unresected colorectal, bladder, noncerebral central nervous system cancers and leukemia, who experienced VTE and received a therapeutic VTE dose of rivaroxaban or apixaban on day 7 post-VTE, and were active in the EHR ≥12 months prior to the VTE. Primary outcome was the composite of recurrent VTE or any bleed resulting in hospitalization at 3 months. Secondary outcomes included recurrent VTE, any bleed resulting in hospitalization, any critical organ bleed, and composites of these outcomes at 3 and 6 months. Inverse probability of treatment-weighted Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). We included 1,344 apixaban and 1,093 rivaroxaban patients. At 3 months, rivaroxaban was found to have similar hazard to apixaban for developing recurrent VTE or any bleed resulting in hospitalization (HR: 0.87; 95% CI: 0.60–1.27). No differences were observed between cohorts for this outcome at 6 months (HR: 1.00; 95% CI: 0.71–1.40) or for any other outcome at 3 or 6 months. In conclusion, patients receiving rivaroxaban or apixaban showed similar risks of the composite of recurrent VTE or any bleed resulting in hospitalization in patients with cancer-associated VTE. This study was registered at as #NCT05461807.

Key Points

  • Rivaroxaban and apixaban have similar effectiveness and safety for treatment of cancer-associated VTE through 6 months.

  • Clinicians should therefore consider patient preference and adherence when choosing the optimal anticoagulant.

a At time of study conduct, currently affiliated with Janssen Research and Development, Barcelona, Spain.

b At time of study conduct, currently consultant for Bayer AG.

Supplementary Material

Publication History

Received: 03 March 2023

Accepted: 17 May 2023

Article published online:
10 July 2023

© 2023. 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. (

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol 2015; 12 (08) 464-474
  • 2 Hutten BA, Prins MH, Gent M, Ginsberg J, Tijssen JG, Büller HR. Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. J Clin Oncol 2000; 18 (17) 3078-3083
  • 3 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
  • 4 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
  • 5 Key NS, Khorana AA, Kuderer NM. et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol 2020; 38 (05) 496-520
  • 6 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
  • 7 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
  • 8 Farge D, Frere C, Connors JM. et al; International Initiative on Thrombosis and Cancer (ITAC) advisory panel. 2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19. Lancet Oncol 2022; 23 (07) e334-e347
  • 9 Streiff MB, Holmstrom B, Angelini D. et al. Cancer-associated venous thromboembolic disease, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2021; 19 (10) 1181-1201
  • 10 Sabatino J, De Rosa S, Polimeni A, Sorrentino S, Indolfi C. Direct oral anticoagulants in patients with active cancer: a systematic review and meta-analysis. JACC Cardiooncol 2020; 2 (03) 428-440
  • 11 Optum. Optum EHR data. 2022. Accessed March 8, 2022 at:
  • 12 White RH, Garcia M, Sadeghi B. et al. Evaluation of the predictive value of ICD-9-CM coded administrative data for venous thromboembolism in the United States. Thromb Res 2010; 126 (01) 61-67
  • 13 Cunningham A, Stein CM, Chung CP, Daugherty JR, Smalley WE, Ray WA. An automated database case definition for serious bleeding related to oral anticoagulant use. Pharmacoepidemiol Drug Saf 2011; 20 (06) 560-566
  • 14 Prasad V, Jena AB. Prespecified falsification end points: can they validate true observational associations?. JAMA 2013; 309 (03) 241-242
  • 15 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
  • 16 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 (Suppl. 01) 2132
  • 17 Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res 2011; 46 (03) 399-424
  • 18 Langan SM, Schmidt SA, Wing K. et al. The reporting of studies conducted using observational routinely collected health data statement for pharmacoepidemiology (RECORD-PE). BMJ 2018; 363: k3532
  • 19 Riaz IB, Fuentes HE, Naqvi SAA. et al. Direct oral anticoagulants compared with dalteparin for treatment of cancer-associated thrombosis: a living, interactive systematic review and network meta-analysis. Mayo Clin Proc 2022; 97 (02) 308-324
  • 20 Lanéelle D, Le Brun C, Mauger C. et al; SFMV VTE Study Group. Patient characteristics and preferences regarding anticoagulant treatment in venous thromboembolic disease. Front Cardiovasc Med 2021; 8: 675969
  • 21 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: 11-13
  • 22 Gandhi SK, Salmon JW, Kong SX, Zhao SZ. Administrative databases and outcomes assessment: an overview of issues and potential utility. J Manag Care Pharm 1999; 5: 215-222