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Prevention of Venous Thromboembolism with New Oral Anticoagulants versus Standard Pharmacological Treatment in Acute Medically Ill Patients

A Systematic Review and Meta-Analysis

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Abstract

Introduction: Venous thromboembolism (VTE) is a common and potentially avoidable cause of morbidity and mortality in patients hospitalized for acute medical illness.

Objective: Our objective was to conduct a systematic review of studies that assessed the efficacy and safety of new oral anticoagulant (OAC) drugs versus standard pharmacological drugs and/or placebo in prevention of VTE in acute medically ill patients.

Methods: PubMed.org and ClinicalTrials.gov databases were searched to identify studies that evaluated the efficacy and safety of a new OAC versus the standard pharmacological treatment and/or placebo in the prevention of VTE in medically ill patients. Relative risks (RR), weighted means and 95% CIs were calculated. Statistical heterogeneity was evaluated using Chi2 and I2 statistics.

Two studies were included in the meta-analysis. The primary outcome in both studies was the composite of VTE-related death, symptomatic non-fatal pulmonary embolism (PE), symptomatic deep venous thrombosis (DVT) and asymptomatic proximal DVT. Both studies compared a factor (F)Xa inhibitor with enoxaparin in standard short-term thromboprophylaxis followed by a period where the FXa inhibitor was compared with placebo as prolonged thromboprophylaxis in medically ill patients. The primary major safety outcome in both studies was a composite of treatment-related major bleeding and clinically relevant non-major bleeding. A total of 14 629 patients were randomized.

Results: Compared with subjects treated with enoxaparin followed by placebo, the RR of the primary outcome during the prolonged treatment period was 0.79 (95% CI 0.66, 0.94), the RR for the primary outcome during the first short-term treatment period was 1.03 (95% CI 0.81, 1.31). For major bleeding during the prolonged treatment period, the RR was 2.69 (95% CI 1.65, 4.39) for patients treated with an FXa inhibitor compared with enoxaparin/placebo. For major bleeding during the shorter treatment period, the RR was 2.01 (95% CI 1.10, 3.65) in favour of enoxaparin.

Conclusion: In acute medically ill patients, prolonged thromboprophylaxis with an oral FXa inhibitor is more protective than regular short-term treatment with enoxaparin. However, treatment with FXa inhibitors is significantly associated with major bleeding, both in long- and short-term treatment compared with enoxaparin.

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Acknowledgements

IEA and TFO have no conflicts of interest. TBL and LHR have served as speakers for BMS/Pfizer and Boehringer Ingelheim. GYHL has served as a consultant for Bayer, Astellas, Merck, AstraZeneca, Sanofi, BMS/Pfizer and Boehringer Ingelheim, and has been on the speaker bureau for Bayer, BMS/Pfizer, Boehringer Ingelheim and Sanofi.

IEA, TBL and GYHL provided the idea for the article and contributed to drafting and subsequent revisions. IEA performed the analyses and contributed to manuscript revisions. LHR and TFO contributed to manuscript drafts, and made critical revisions for important intellectual content. The authors take full responsibility for the content of the article.

No funding was received for the preparation of this review. This study was conducted fully independent of any industry or other grant support.

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Authors and Affiliations

  1. City Hospital, University of Birmingham Centre for Cardiovascular Sciences, Birmingham, B18 7QH, UK

    Ida Ehlers Albertsen, Thure Filskov Overvad &  Gregory Y. H. Lip

  2. Department of Cardiology, Aalborg AF Study Group, Cardiovascular Research Centre, Aalborg Hospital, Aalborg, Denmark

    Ida Ehlers Albertsen, Torben Bjerregaard Larsen & Thure Filskov Overvad

  3. Thrombosis Research Unit, Aalborg University, Aalborg, Denmark

    Torben Bjerregaard Larsen, Lars Hvilsted Rasmussen &  Gregory Y. H. Lip

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  1. Ida Ehlers Albertsen
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Correspondence to Gregory Y. H. Lip.

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Albertsen, I.E., Larsen, T.B., Rasmussen, L.H. et al. Prevention of Venous Thromboembolism with New Oral Anticoagulants versus Standard Pharmacological Treatment in Acute Medically Ill Patients. Drugs 72, 1755–1764 (2012). https://doi.org/10.2165/11635630-000000000-00000

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