Effectiveness and safety of betrixaban extended prophylaxis for venous thromboembolism compared with standard-duration prophylaxis intervention in acute medically ill patients: a systematic literature review and network meta-analysis

Abstract

Aims: To determine the clinical effectiveness and safety of venous thromboembolism (VTE) prophylaxis using US- and Europe-approved anticoagulants relative to extended-duration VTE prophylaxis with betrixaban. Low molecular weight heparins (LMWHs), unfractionated heparin (UFH), fondaparinux sodium and placebo were each compared to betrixaban, as standard-duration VTE prophylaxis for hospitalized, non-surgical patients with acute medical illness at risk of VTE.

Materials and methods: A systematic literature review was conducted up to June 2019 to identify randomized controlled trials (RCTs) of VTE prophylaxis in hospitalized, non-surgical patients with acute medical illness at risk of VTE. Studies that reported the occurrence of VTE events (including death) and, where possible, major bleeding, from treatment initiation to 20–50 days thereafter were retrieved and extracted. A Bayesian fixed effect network meta-analysis was used to estimate efficacy and safety of betrixaban compared with standard-duration VTE prophylaxis.

Results: Seven RCTs were analyzed which compared betrixaban, LMWHs, UFH, fondaparinux sodium, or placebo. There were significantly higher odds (median odds [95% credible interval]) of VTE with LMWHs (1.38 [1.12–1.70]), UFH (1.60 [1.05–2.46]), and placebo (2.37 [1.55–3.66]) compared with betrixaban. There were significantly higher odds of VTE-related death with placebo (7.76 [2.14–34.40]) compared with betrixaban. No significant differences were observed for the odds of major bleeding with all comparators, VTE-related death with any active standard-duration VTE prophylaxis, or of VTE with fondaparinux sodium, compared with betrixaban.

Limitations and conclusions: In this indirect comparison, betrixaban was shown to be an effective regimen with relative benefits compared with LMWHs and UFH. This indicates that betrixaban could reduce the burden of VTE in at-risk hospitalized patients with acute medical illness who need extended prophylaxis, though without direct comparative evidence, stronger conclusions cannot be drawn.

Keywords:

• Venous thromboembolism
• pre-exposure thromboprophylaxis
• network meta-analysis
• primary thromboprophylaxis
• betrixaban

JEL CLASSIFICATION CODES:

• C11
• C10

Transparency

Declaration of funding

This research was supported by Portola Pharmaceuticals, Inc.

Declaration of financial/other relationships

VL, HG, and MF are employees of FIECON Ltd, a health-economics outcomes research agency, which performed the analyses presented in the manuscript, funded by Portola Pharmaceuticals, Inc. RN and IB were employees of Portola Pharmaceuticals, Inc, at the time of the research project. SR is a Research Fellow at The University of Sheffield and performed the analyses presented in the manuscript in collaboration with FIECON Ltd, funded by FIECON Ltd. ATC has received consulting fees, research support, and honoraria from AbbVie, ACI Clinical, Aspen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Boston Scientific, CSL Behring, Daiichi-Sankyo, GlaxoSmithKline, GLG, Guidepoint Global, Johnson and Johnson, Leo Pharma, Medscape, McKinsey, Navigant, ONO, Pfizer, Portola, Sanofi, Takeda, Temasek Capital, and TRN. A peer reviewer on this manuscript has disclosed receiving grants and honoraria from various pharma companies, including those developing, manufacturing, and marketing anti-coagulants. The peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Acknowledgements

Augusta Connor is thanked for her editing to bring the publication to press.

Previous presentations

The base case results were presented in a poster submitted to both the American College of Clinical Pharmacy (ACCP) and the Academy of Managed Care Pharmacy in 2018. The abstract for the poster was published in the abstract book of the conference of ACCP. There has not yet been a full publication of the results.

Data availability statement

Raw data were generated at Portola Pharmaceuticals. Derived data supporting the findings of this study are available from the corresponding author (VL) on request.