A systematic review of apixaban in prevention and treatment of cancer-associated venous thromboembolism



      Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer after disease progression. Thus, timely initiation of anticoagulation after diagnosis of a VTE is required to prevent significant sequelae. Direct oral anticoagulants (DOACs) are newer anticoagulant options for cancer associated VTE (CA-VTE), which historically has been treated with low molecular weight heparin.


      The objective of this study was to review the available literature evaluating the use of apixaban for CA-VTE.


      A systematic review (following PRISMA Guidelines) of MEDLINE and EMBASE using the search terms “apixaban” AND “cancer” AND “VTE” was performed from database inception through May 20, 2020. Articles were eligible for inclusion if they were full articles fulfilling the following criteria: (1) randomized controlled trial (RCT) or prospective cohort study, or (2) subgroup analysis of an RCT, and (3) reported clinical outcomes associated with apixaban for prevention or treatment of VTE in patients with cancer.


      A total of 532 articles were identified. After duplicates were removed, 423 articles were screened, and 12 articles were eligible for full-text review. Of the 12 articles, 2 were excluded for having no comparator group, and 2 were excluded for being abstracts only. Ultimately, 8 articles met the inclusion criteria.


      The available literature supports the safety and efficacy of apixaban for the treatment and prevention of CA-VTE. With the recent publication of the CARAVAGGIO trial, we anticipate that apixaban will be uniformly recommended in national guidelines as a treatment option for CA-VTE.
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        • Farge D.
        • Frere C.
        • Connors J.M.
        • et al.
        2019 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer.
        Lancet Oncol. 2019; 20: e566-e581
        • Lee A.Y.
        • Levine M.N.
        • Baker R.I.
        • et al.
        Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.
        N Engl J Med. 2003; 349: 146-153
        • Meyer G.
        • Marjanovic Z.
        • Valcke J.
        • et al.
        Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study.
        Arch Intern Med. 2002; 162: 1729-1735
        • Hull R.D.
        • Pineo G.F.
        • Brant R.F.
        • et al.
        Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer.
        Am J Med. 2006; 119: 1062-1072
        • Deitcher S.R.
        • Kessler C.M.
        • Merli G.
        • et al.
        Secondary prevention of venous thromboembolic events in patients with active cancer: enoxaparin alone versus initial enoxaparin followed by warfarin for a 180-day period.
        Clin Appl Thromb Hemost. 2006; 12: 389-396
        • Young A.M.
        • 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: 2017-2023
        • Raskob G.E.
        • van Es N.
        • Verhamme P.
        • et al.
        Edoxaban for the treatment of cancer-associated venous thromboembolism.
        N Engl J Med. 2018; 378: 615-624
        • Key N.S.
        • Khorana A.A.
        • Kuderer N.M.
        • et al.
        Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update.
        J Clin Oncol. 2020; 38: 496-520
      1. National Comprehensive Cancer Network. NCCN Guidelines Insights: Cancer-Associated Venous Thromboembolic Disease, Version 2.2018. J Natl Compr Canc Netw. 2018;16(11):1289-1303.

        • Agnelli G.
        • Buller H.R.
        • Cohen A.
        • et al.
        Oral apixaban for the treatment of venous thromboembolism in cancer patients: results from the AMPLIFY trial.
        J Thromb Haemost. 2015; 13: 2187-2191
        • Lekura J.
        Safety and efficacy of target-specific anticoagulation in patients with venous thromboembolism.
        Ann Pharmacother. 2015; 49: 448-457
        • Khorana A.A.
        • Soff G.A.
        • Kakkar A.K.
        • et al.
        Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer.
        N Engl J Med. 2019; 380: 720-728
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        • PRISMA Group
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        PLoS Med. 2009; 6e1000097
        • Levine M.N.
        • Gu C.
        • Liebman H.A.
        • et al.
        A randomized phase II trial of apixaban for prevention of thromboembolism in patients with metastatic cancer.
        J Thromb Haemost. 2012; 10: 807-814
        • Carrier M.
        • Abou-Nassar K.
        • Mallick R.
        • et al.
        Apixaban to prevent venous thromboembolism in patients with cancer.
        N Engl J Med. 2019; 380: 711-719
        • Knoll W.
        • Mallick R.
        • Wells P.S.
        • Carrier M.
        Safety and efficacy of apixaban thromboprophylaxis in cancer patients with metastatic disease: a subgroup analysis of the avert trial.
        Blood. 2019; 134: 1140
        • Atalla M.
        • Zhang J.
        • Mallick R.
        • et al.
        Thromboprophylaxis for patients with newly diagnosed vs. recurrent cancers: a post-hoc analysis of the avert trial.
        Blood. 2019; 51: 3660
        • Agnelli G.
        • Buller H.R.
        • Cohen A.
        • et al.
        Oral apixaban for the treatment of acute venous thromboembolism.
        N Engl J Med. 2013; 369: 799-808
        • Lee A.Y.Y.
        • Kamphuisen P.W.
        • Meyer G.
        • et al.
        Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: a randomized clinical trial [published correction appears in JAMA. 2017;318(20):2048].
        JAMA. 2015; 314: 677-686
        • Wysokinski W.E.
        • Houghton D.E.
        • Casanegra A.I.
        • et al.
        Comparison of apixaban to rivaroxaban and enoxaparin in acute cancer-associated venous thromboembolism.
        Am J Hematol. 2019; 94: 1185-1192
        • McBane R.D.
        • Wysokinski W.E.
        • Le-Rademacher J.G.
        • et al.
        Apixaban and dalteparin in active malignancy-associated venous thromboembolism: the ADAM VTE trial.
        J Thromb Haemost. 2020; 18: 411-421
        • Agnelli G.
        • Becattini C.
        • Meyer G.
        • et al.
        Apixaban for the treatment of venous thromboembolism associated with cancer.
        N Engl J Med. 2020; 382: 1599-1607


      Ryan Caputo, PharmD, Pharmacy Resident, Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, OH


      Jacqueline Pyle, PharmD, BCCP, Clinical Pharmacist, Department of Pharmacy Services, Henry Ford Hospital, Detroit, MI


      Philip Kuriakose, MD, Medical Doctor, Hematologist, Division of Hematology/Oncology, Henry Ford Cancer Institute, Henry Ford Hospital, Detroit, MI


      Jona Lekura, PharmD, BCPS, Clinical Pharmacy Specialist, Department of Pharmacy Services, Henry Ford Hospital, Detroit, MI