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DOAC compared to LMWH in the treatment of cancer related-venous thromboembolism: a systematic review and meta-analysis

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Abstract

Low molecular weight heparins (LMWH) are the standard of care for the treatment of cancer-associated venous thromboembolism (CA-VTE). We performed a systematic review and meta-analysis to compare the effects of direct oral anticoagulants (DOAC) versus LMWH for the treatment of CA-VTE. The primary efficacy and safety outcomes were VTE recurrence and major bleeding (MB). The secondary outcomes were clinically relevant non-MB (CRNMB), all-cause mortality and the net clinical benefit. We searched MEDLINE, EMBASE, CENTRAL and Web of Science (inception-December 2019) and abstracts of relevant conferences (2000–2019) to identify randomized controlled trials comparing DOAC and LMWH for the treatment of CA-VTE. Relative risks (RR) and 95% confidence intervals were estimated (Mantel–Haenszel method, random-effects models). A non-inferiority analysis with a margin of 1.3 for the upper boundary of the RR was conducted for the primary outcomes. From 637 references, we included four publications which encompass three trials (1756 patients). Compared to LMWH, DOAC were associated with a trend for decreased VTE recurrence (RR 0.51; 95%CI 0.25–1.03; p = 0.06; I2 = 51%), whereas MB (RR 1.64; 95%CI 1.00–2.69; p = 0.05; I2 = 0%) and CRNMB (RR 1.83; 95%CI 1.04–3.20; p = 0.03; I2 = 50%) were significantly more frequent with DOAC. Conversely, all-cause mortality (RR 1.06; 95%CI 0.83–1.35; p = 0.64; I2 = 36%) and net clinical benefit (RR 0.74; 95%CI 0.38–1.42; p = 0.36; I2 = 65%) were comparable. DOAC were non-inferior to LMWH in preventing CA-VTE recurrence, but were associated with an increased risk of MB and CRNMB. Further studies are required to confirm these results and inform on the risk/benefit ratio for specific populations.

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Acknowledgements

The authors thank Caroline Lambert and Sylvie Martin for significant technical assistance, as well as Mrs Sarah O’Conner Dt.P. for her methodological help

Funding

No funding was received to perform this systematic review and meta-analysis.

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Authors and Affiliations

  1. Institut Universitaire de Cardiologie Et de Pneumologie de Québec Research Center, Laval University, Quebec, Canada

    V. Mai, V. F. Tanguay, C. A. Guay, Y. Lacasse & S. Provencher

  2. Service de Médecine Vasculaire Et Thérapeutique, UMR 1059, SAINBIOSE and CIC 1408, CHU de St-Etienne, INSERM, St-Etienne, France

    L. Bertoletti

  3. Université Jean-Monnet, St-Etienne, France

    L. Bertoletti

  4. Department of Medicine, CHU de Québec, Université Laval, Quebec, QC, Canada

    S. Magnan, Y. Lacasse & S. Provencher

  5. Trauma - Emergency - Critical Care Medicine, CHU de Québec – Université Laval Research Centre, Population Health and Optimal Health Practices Research Unit, Université Laval, Quebec, QC, Canada

    A. F. Turgeon

  6. Division of Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Université Laval, Quebec, QC, Canada

    A. F. Turgeon

  7. UMR 5558, Laboratoire de Biométrie Et Biologie Evolutive, Groupe D’Etude Multidisciplinaire Des Maladies Thrombotiques (GEMMAT), Univ Lyon, CNRS, University of Lyon, 69003, Pierre-Bénite, France

    J. C. Lega

  8. Department of Internal and Vascular Medicine, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, 69310, Pierre-Bénite, France

    J. C. Lega

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  1. V. Mai
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  2. V. F. Tanguay
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  3. C. A. Guay
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  4. L. Bertoletti
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  7. Y. Lacasse
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  8. J. C. Lega
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  9. S. Provencher
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Corresponding author

Correspondence to S. Provencher.

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Conflict of interest

LB has received speaker and consultant fees from Aspen, Bayer, BMS-Pfizer and Daiichi-Sankyo, outside the submitted work. JCL has received speaker and consultant fees from Boerhinger-Ingelheim, Bayer, BMS-Pfizer and Daiichi-Sankyo, and having received research grants from BMS-Pfizer, outside the submitted work. SP is clinician-scientist of the Fonds de Recherche du Québec—Santé and has received research grants from Actelion Pharmaceuticals and Boehringer-Ingelheim, outside the submitted work. AFT is the Canada Research Chair in Critical Care Neurology and Trauma. He has no conflict of interest to declare. VM, VFT, CAG, SM and YL have no conflict of interest to declare.

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Mai, V., Tanguay, V.F., Guay, C.A. et al. DOAC compared to LMWH in the treatment of cancer related-venous thromboembolism: a systematic review and meta-analysis. J Thromb Thrombolysis 50, 661–667 (2020). https://doi.org/10.1007/s11239-020-02055-1

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