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Thromb Haemost 2020; 120(07): 1128-1136
DOI: 10.1055/s-0040-1712098
Stroke, Systemic or Venous Thromboembolism
Georg Thieme Verlag KG Stuttgart · New York

Direct Oral Anticoagulants for the Treatment of Acute Venous Thromboembolism Associated with Cancer: A Systematic Review and Meta-Analysis

Michela Giustozzi 
1   Internal Vascular and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy
,
Giancarlo Agnelli
1   Internal Vascular and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy
,
Jorge del Toro-Cervera
2   Medicina Interna – Unidad de ETV, Hospital Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain
,
Frederikus A. Klok 
3   Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
,
Rachel P. Rosovsky
4   Hematology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Anne-Céline Martin
5   Hôpital Européen Georges Pompidou, Service de Cardiologie, F-75015, Paris, France
6   Innovations Thérapeutiques en Hémostase, Université de Paris, INSERM, F-75006 Paris, France
,
Joerg Herold
7   Department of Vascular Medicine, Technische Universität Darmstadt, Darmstadt, Germany
,
Inna Tzoran
8   Institute of Hematology and BMT Rambam Health Care Campus, Technion – Israel Institute of Technology, Haifa, Israel
,
Sebastian Szmit
9   Department of Pulmonary Circulation, Thromboembolic Diseases and Cardiology, Centre of Postgraduate Medical Education, European Health Centre, Otwock, Poland
,
Laurent Bertoletti 
10   Service de Médecine Vasculaire et Thérapeutique, CHU de St-Etienne, INSERM, UMR1059, Université Jean-Monnet, INSERM, CIC-1408, CHU Saint-Etienne, and INNOVTE, F-42055, Saint-Etienne, France
,
Cecilia Becattini
1   Internal Vascular and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy
,
Menno V. Huisman
3   Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
› Author Affiliations Funding None.
Further Information

Publication History

31 March 2020

23 April 2020

Publication Date:
04 May 2020 (online)

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Abstract

Background International guidelines have endorsed the use of edoxaban or rivaroxaban as an alternative to low-molecular-weight heparin (LMWH) for the treatment of acute venous thromboembolism (VTE) in cancer patients. Recently, a large randomized controlled trial of apixaban versus dalteparin in patients with cancer was completed. We performed an updated meta-analysis to assess the efficacy and safety of direct oral anticoagulants (DOACs) versus LMWH in patients with cancer-associated VTE.

Methods MEDLINE, EMBASE, and CENTRAL (Cochrane Controlled Trials Registry) were systematically searched up to March 30, 2020 for randomized controlled trials comparing DOACs versus LMWH for the treatment of VTE in patients with cancer. The two coprimary outcomes were recurrent VTE and major bleeding at 6 months. Data were pooled by the Mantel–Haenszel method and compared by relative risk ratios (RRs) and 95% confidence intervals (CIs).

Results Four randomized controlled studies (2,894 patients) comparing apixaban, edoxaban, or rivaroxaban with dalteparin were included in the meta-analysis. Recurrent VTE occurred in 75 of 1,446 patients (5.2%) treated with oral factor Xa inhibitors and in 119 of 1,448 patients (8.2%) treated with LMWH (RR 0.62; 95% CI 0.43–0.91; I 2, 30%). Major bleeding occurred in 62 (4.3%) and 48 (3.3%) patients receiving oral factor Xa inhibitors or LMWH, respectively (RR 1.31; 95% CI 0.83–2.08; I 2, 23%).

Conclusion In patients with cancer-associated VTE, oral factor Xa inhibitors reduced the risk of recurrent VTE without a significantly higher likelihood of major bleeding at 6 months compared with LMWH.

Keywords

direct oral anticoagulants - oral factor Xa inhibitors - cancer - dalteparin - meta-analysis - venous thromboembolism

Supplementary Material

 

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