Skip to main content
SpringerLink
Log in

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

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Heit JA, Spencer FA, White RH (2016) The epidemiology of venous thromboembolism. J Thromb Thrombolysis 41(1):3–14. doi:10.1007/s11239-015-1311-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kahn SR, Lim W, Dunn AS, Cushman M, Dentali F, Akl EA, Cook DJ, Balekian AA, Klein RC, Le H, Schulman S, Murad MH, American College of Chest Physicians (2012) Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 141(2 Suppl):e195S-226S. doi:10.1378/chest.11-2296.

    Google Scholar 

  3. Amin AN, Varker H, Princic N, Lin J, Thompson S, Johnston S (2012) Duration of venous thromboembolism risk across a continuum in medically ill hospitalized patients. J Hosp Med 7(3):231–238. doi:10.1002/jhm.1002

    Article  PubMed  Google Scholar 

  4. Goldhaber SZ, Leizorovicz A, Kakkar AK, Haas SK, Merli G, Knabb RM, Weitz JI, ADOPT Trial Investigators (2011) Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med 365(23):2167–2177. doi:10.1056/NEJMoa1110899

    Article  CAS  PubMed  Google Scholar 

  5. Cohen AT, Spiro TE, Buller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos AC, Tapson V, MAGELLAN Investigators (2013) Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med 368(6):513–523. doi:10.1056/NEJMoa1111096

    Article  CAS  PubMed  Google Scholar 

  6. Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, Hernandez AF, Gibson CM, APEX Investigators (2016) Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients. N Engl J Med 375(6):534–544. doi:10.1056/NEJMoa1601747

    Article  CAS  PubMed  Google Scholar 

  7. Cohen AT, Bailey CS, Alikhan R, Cooper DJ (2001) Extended thromboprophylaxis with low molecular weight heparin reduces symptomatic venous thromboembolism following lower limb arthroplasty—a meta-analysis. Thromb Haemost 85(5):940–941

    CAS  PubMed  Google Scholar 

  8. Raskob GE, Gallus AS, Pineo GF, Chen D, Ramirez LM, Wright RT, Lassen MR (2012) Apixaban versus enoxaparin for thromboprophylaxis after hip or knee replacement: pooled analysis of major venous thromboembolism and bleeding in 8464 patients from the ADVANCE-2 and ADVANCE-3 trials. J Bone Joint Surg Br 94(2):257–264. doi:10.1302/0301-620X.94B2.27850

    Article  CAS  PubMed  Google Scholar 

  9. Turpie AG, Lassen MR, Eriksson BI, Gent M, Berkowitz SD, Misselwitz F, Bandel TJ, Homering M, Westermeier T, Kakkar AK (2011) Rivaroxaban for the prevention of venous thromboembolism after hip or knee arthroplasty. Pooled analysis of four studies. Thromb Haemost 105(3):444–453. doi:10.1160/TH10-09-0601

    Article  CAS  PubMed  Google Scholar 

  10. Schulman S, Majeed A (2011) A benefit-risk assessment of dabigatran in the prevention of venous thromboembolism in orthopaedic surgery. Drug Saf 34(6):449–463. doi:10.2165/11587290-000000000-00000

    Article  CAS  PubMed  Google Scholar 

  11. Hull RD, Schellong SM, Tapson VF, Monreal M, Samama MM, Nicol P, Vicaut E, Turpie AG, Yusen RD, study E (2010) Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med 153(1):8–18. doi:10.7326/0003-4819-153-1-201007060-00004

    Article  PubMed  Google Scholar 

  12. Cohen AT, Halaby R, Korjian S, Daaboul Y, Szlosek D, Arbetter D, Goldhaber SZ, Hull R, Hernandez A, Gold A, Wiens B, Harrington R, Gibson CM (2016) The safety and efficacy of full versus reduced dose betrixaban in the acute medically Ill VTE (venous thromboembolism) prevention with extended duration betrixaban (APEX) trial. Am Heart J 185:93–100

    PubMed  Google Scholar 

  13. Jain P, Szlosek DA, Korjian S, Daaboul Y, Lopes RD, Goldhaber SZ, Hernandez AF, Hull RD, Harrington RA, Cohen AT, Gibson CM (2016) Abstract 19325: betrixaban reduces the burden of multiple symptomatic venous thromboembolic events in the APEX trial. Circulation 134(Suppl 1):A19325

    Google Scholar 

  14. Gibson CM, Chi G, Halaby R, Korjian S, Daaboul Y, Jain P, Arbetter D, Goldhaber SZ, Hull R, Hernandez AF, Gold A, Bandman O, Harrington RA, Cohen AT, APEX Investigators (2016) Extended-duration betrixaban reduces the risk of stroke versus standard-dose enoxaparin among hospitalized medically Ill patients: an APEX trial substudy (acute medically Ill venous thromboembolism prevention with extended duration betrixaban). Circulation. doi:10.1161/CIRCULATIONAHA.116.025427

    Google Scholar 

  15. Tao DL, Bien JY, DeLoughery TG, Shatzel JJ (2016) Extended thromboprophylaxis with direct oral anticoagulants for medical patients: A systematic review & meta-analysis. Blood. doi:10.1182/blood-2016-10-747931

    PubMed  Google Scholar 

  16. Liew AY, Piran S, Eikelboom JW, Douketis JD (2016) Extended-duration versus short-duration pharmacological thromboprophylaxis in acutely Ill hospitalized medical patients: a systematic review and meta-analysis of randomized controlled trials. J Thromb Thrombolysis. doi:10.1007/s11239-016-1461-1

    Google Scholar 

  17. Sqizzato A, Ageno W (2014) A new era for venous thromboembolism prevention in medical inpatients. Thromb Haemost 112:627–628

    Article  Google Scholar 

  18. Raskob GE, Spyropoulos AC, Zrubek J, Ageno W, Albers G, Elliott CG, Halperin J, Haskell L, Hiatt WR, Maynard GA, Peters G, Spiro T, Steg PG, Suh EY, Weitz JI (2016) The MARINER trial of rivaroxaban after hospital discharge for medical patients at high risk of VTE. Design, rationale, and clinical implications. Thromb Haemost 115(5). doi:10.1160/TH15-09-0756

Download references

Author information

Authors and Affiliations

  1. Center for Health Outcomes and PharmacoEconomic Research, University of Arizona, 1295 N. Martin, P.O. Box 210202, Tucson, AZ, 85721-0202, USA

    Majed S. Al Yami, Osamah M. Alfayez, Sawsan M. Kurdi & Razan Alsheikh

  2. King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia

    Majed S. Al Yami

  3. Qassim University, Qassim, Saudi Arabia

    Osamah M. Alfayez

  4. University of Dammam, Dammam, Saudi Arabia

    Sawsan M. Kurdi

  5. King Abdulaziz University, Jeddah, Saudi Arabia

    Razan Alsheikh

Authors
  1. Majed S. Al Yami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Osamah M. Alfayez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sawsan M. Kurdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Razan Alsheikh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Majed S. Al Yami.

Ethics declarations

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Al Yami, M.S., Alfayez, O.M., Kurdi, S.M. et al. Direct oral anticoagulants for extended-duration thromboprophylaxis in hospitalized medically ill patients: are we there yet?. J Thromb Thrombolysis 44, 1–8 (2017). https://doi.org/10.1007/s11239-017-1481-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-017-1481-5

Keywords

Search

Navigation