Direct oral anticoagulants for extended-duration thromboprophylaxis in hospitalized medically ill patients: are we there yet?

  • Majed S. Al YamiEmail author
  • Osamah M. Alfayez
  • Sawsan M. Kurdi
  • Razan Alsheikh


Despite a recommended 7–10 days of thromboprophylaxis, medically ill patients remain at increased risk of developing venous thromboembolism (VTE) after hospital discharge. Here, we present a contemporary review on the efficacy and safety of extended-duration thromboprophylaxis with direct oral anticoagulants (DOACs) in hospitalized medically ill patients. A search of publication and trial databases of controlled trials conducted from 2010 to 2016 using the key terms apixaban, rivaroxaban, and betrixaban showed three phase III trials that met our search criteria. In the “ADOPT” trial, apixaban was not inferior to enoxaparin in preventing VTE events (relative risk [RR] of 0.87; 95% confidence interval [CI] 0.62–1.23; P = 0.44); however, major bleeding rate was significantly higher with apixaban (RR of 2.58; 95% CI 1.02–7.24; P = 0.04). In the “MAGELLAN” trial, rivaroxaban was superior to enoxaparin in preventing VTE events (RR of 0.77; 95% CI 0.62–0.96; P = 0.02) but with higher clinically relevant bleeding rate (RR of 2.5; 95% CI 1.85–3.25; P < 0.001). Finally, in the “APEX” trial, there were no differences between betrixaban and enoxaparin in preventing VTE events in patients with elevated D-dimer levels (RR of 0.81; 95% CI 0.65–1.00; P = 0.054) and no differences in major bleeding events in all patients (RR of 1.19; 95% CI 0.67–2.12; P = 0.55). Compared with standard-duration thromboprophylaxis with enoxaparin, extended-duration thromboprophylaxis with DOACs in medically ill patients may provide an incremental benefit, although at the cost of increased bleeding events.


Apixaban Betrixaban Enoxaparin Rivaroxaban Thromboprophylaxis Medically Ill Patients 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animal performed by any of the authors.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Majed S. Al Yami
    • 1
    • 2
    Email author
  • Osamah M. Alfayez
    • 1
    • 3
  • Sawsan M. Kurdi
    • 1
    • 4
  • Razan Alsheikh
    • 1
    • 5
  1. 1.Center for Health Outcomes and PharmacoEconomic ResearchUniversity of ArizonaTucsonUSA
  2. 2.King Saud bin Abdulaziz University for Health SciencesRiyadhSaudi Arabia
  3. 3.Qassim UniversityQassimSaudi Arabia
  4. 4.University of DammamDammamSaudi Arabia
  5. 5.King Abdulaziz UniversityJeddahSaudi Arabia

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