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

Kimberly Snow Caroti, Cecilia Becattini, Marc Carrier, Alexander T Cohen, Anders Ekbom, Alok A Khorana, Agnes Y Y Lee, Christopher Brescia, Khaled Abdelgawwad, George Psaroudakis, Marcela Rivera, Bernhard Schaefer, Gunnar Brobert, Craig I Coleman, Kimberly Snow Caroti, Cecilia Becattini, Marc Carrier, Alexander T Cohen, Anders Ekbom, Alok A Khorana, Agnes Y Y Lee, Christopher Brescia, Khaled Abdelgawwad, George Psaroudakis, Marcela Rivera, Bernhard Schaefer, Gunnar Brobert, Craig I Coleman

Abstract

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 www.clinicaltrials.gov 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.

Keywords: apixaban; cancer-associated VTE; rivaroxaban; venous thromboembolism.

Conflict of interest statement

Conflict of Interest K.S. Caroti reports no conflicts of interest. A.A. Khorana reports consulting fees, honoraria, and travel support from Bayer AG, consulting fees, honoraria, and travel support from Janssen, consulting fees and honoraria from Bristol Myers Squibb, consulting fees and honoraria from Anthos, consulting fees and honoraria from Pfizer, consulting fees and honoraria from Sanofi, and honoraria from WebMD. C. Becattini reports consulting fees and honoraria from Bayer AG, consulting fees and honoraria from Bristol Myers Squibb, consulting fees and honoraria from Daiichi Sankyo, and consulting fees from Pfizer. A.Y.Y. Lee reports consulting fees and honoraria from Bayer AG, consulting fees and honoraria from LEO Pharma, consulting fees and honoraria from Pfizer, consulting fees from Servier, and honoraria from Bristol Myers Squibb. A. Ekbom reports no conflicts of interest. M. Carrier reports grants and consulting fees from Pfizer, grants and consulting fees from LEO Pharma, grants and consulting fees from Bristol Myers Squibb, consulting fees from Bayer AG, consulting fees from Sanofi, and consulting fees from Servier. A.T. Cohen reports grants, consulting fees, and honoraria from Alexion/AstraZeneca, grants, consulting fees, and honoraria from Bristol Myers Squibb/Pfizer, and consulting fees and honoraria from Bayer AG. C. Brescia reports no conflicts of interest. K. Abdelgawwad and G. Psaroudakis are employees of Bayer AG. M. Rivera was an employee of Bayer AG at the time of study conduct and is currently an employee of Janssen Research and Development. B. Schaefer is an employee of Bayer AG. G. Brobert is a consultant for Bayer AG. C.I. Coleman reports grants, consulting fees, and travel support from Bayer AG, grants and consulting fees from Janssen Pharmaceuticals, grants and consulting fees from Alexion Pharmaceutical, and honoraria from Medscape.

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/ ).

Figures

Fig. 1
Fig. 1
Patient inclusion and exclusion from the study. Of 14,618 patients with Ca-VTE initially identified, 12,181 were excluded, resulting in a final study population of 2,437 patients with cancer types for which oral factor Xa inhibitors are recommended according to guidelines and receiving either rivaroxaban or apixaban for inclusion in the analysis. Ca-VTE, cancer-associated venous thromboembolism; CNS, central nervous system.
Fig. 2
Fig. 2
Time to recurrent VTE or bleeding-related hospitalization in rivaroxaban and apixaban patients. Kaplan–Meier curve for the composite of recurrent VTE or bleeding-related hospitalization (rivaroxaban = solid line, apixaban = dashed line). VTE, venous thromboembolism.
Fig. 3
Fig. 3
Time to pneumonia (falsification outcome) in rivaroxaban and apixaban patients with Ca-VTE. Kaplan–Meier curve for the falsification outcome of pneumonia (rivaroxaban = solid line, apixaban = dashed line). Ca-VTE, cancer-associated venous thromboembolism.

References

    1. Heit J A. Epidemiology of venous thromboembolism. Nat Rev Cardiol. 2015;12(08):464–474.
    1. Hutten B A, Prins M H, Gent M, Ginsberg J, Tijssen J G, Büller H R. 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.
    1. Prandoni P, Lensing A WA, Piccioli A. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002;100(10):3484–3488.
    1. Khorana A A, Noble S, Lee A YY. 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.
    1. Key N S, Khorana A A, Kuderer N M. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2020;38(05):496–520.
    1. ESC Scientific Document Group . Konstantinides S V, Meyer G, Becattini C. 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.
    1. Lyman G H, Carrier M, Ay C. 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.
    1. International Initiative on Thrombosis and Cancer (ITAC) advisory panel . Farge D, Frere C, Connors J M. 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.
    1. Streiff M B, Holmstrom B, Angelini D. Cancer-associated venous thromboembolic disease, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2021;19(10):1181–1201.
    1. 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.
    1. Optum. Optum EHR data. 2022. Accessed March 8, 2022 at:
    1. White R H, Garcia M, Sadeghi B. 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.
    1. Cunningham A, Stein C M, Chung C P, Daugherty J R, Smalley W E, Ray W A. An automated database case definition for serious bleeding related to oral anticoagulant use. Pharmacoepidemiol Drug Saf. 2011;20(06):560–566.
    1. Prasad V, Jena A B. Prespecified falsification end points: can they validate true observational associations? JAMA. 2013;309(03):241–242.
    1. Hokusai VTE Cancer Investigators . Raskob G E, van Es N, Verhamme P. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med. 2018;378(07):615–624.
    1. Coleman C, Caroti K S, Abdelgawwad K. 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.
    1. Austin P C. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res. 2011;46(03):399–424.
    1. Langan S M, Schmidt S A, Wing K. The reporting of studies conducted using observational routinely collected health data statement for pharmacoepidemiology (RECORD-PE) BMJ. 2018;363:k3532.
    1. Riaz I B, Fuentes H E, Naqvi S AA. 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.
    1. SFMV VTE Study Group . Lanéelle D, Le Brun C, Mauger C. Patient characteristics and preferences regarding anticoagulant treatment in venous thromboembolic disease. Front Cardiovasc Med. 2021;8:675969.
    1. Alberts M J, Peacock W F, Fields L E. 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.
    1. Gandhi S K, Salmon J W, Kong S X, Zhao S Z. Administrative databases and outcomes assessment: an overview of issues and potential utility. J Manag Care Pharm. 1999;5:215–222.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe