Skip to main content
SpringerLink
Log in

Effects of body mass index on the safety and effectiveness of direct oral anticoagulants: a retrospective review

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

Abstract

Background

The International Society on Thrombosis and Haemostasis recommends avoiding the use of direct oral anticoagulants (DOACs) in patients with a body mass index (BMI) greater than 40 kg/m2 or weight greater than 120 kg.

Hypothesis

Higher BMI is associated with altered pharmacokinetics which may affect the safety and effectiveness for DOACs.

Methods

Data were collected on 3458 patients taking a DOAC prior to admission to a Midwestern health system between February 2013 and August 2016. Of these, 43 patients had a thrombotic event and 70 patients had an overt bleeding event. Patients were stratified among the following three BMI groups: BMI < 30 kg/m2, BMI 30–40 kg/m2, and BMI > 40 kg/m2.

Results

There was no statistically significant difference between BMI groups for thrombotic events (p = 0.598) or for overt bleeding events (p = 0.065). The BMI < 30 kg/m2 had the highest occurrence rate of bleeding events. It was observed that bleeding occurrence decreased as the BMI groups increased. The BMI > 40 kg/m2 group had the lowest risk of bleeding events, and was the only group to have a higher occurrence rate of thrombotic events compared to bleeding events.

Conclusions

Among patients admitted to a single health system on DOAC therapy over a three-and-a-half-year period, obesity did not significantly correlate with thrombotic or overt bleeding complications. This study is limited as a single health system study with low overall event rates. A preliminary finding of this study showed a trend towards decreased bleeding frequency as BMI increased.

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

Fig. 1

Similar content being viewed by others

References

  1. Kearon C, Akl EA, Ornelas J et al (2016) Antithrombotic therapy for VTE disease: chest guideline and expert panel report. Chest 149(2):315–352

    Article  PubMed  Google Scholar 

  2. January CT, Wann LS, Alpert JS et al (2014) 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 130(23):2071–2104

    Article  PubMed  Google Scholar 

  3. Hirschl M, Kundi M (2014) New oral anticoagulants in the treatment of acute venous thromboembolism - a systematic review with indirect comparisons. VASA. 43(5):353–364

    Article  PubMed  Google Scholar 

  4. Larsen TB, Skjøth F, Nielsen PB, Kjældgaard JN, Lip GY (2016) Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ 353:i3189

    Article  PubMed  PubMed Central  Google Scholar 

  5. Hellenbart EL, Faulkenberg KD, Finks SW (2017) Evaluation of bleeding in patients receiving direct oral anticoagulants. Vasc Health Risk Manag. 13:325–342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hanley MJ, Abernethy DR, Greenblatt DJ (2010) Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet 49(2):71–87

    Article  CAS  PubMed  Google Scholar 

  7. Martin K, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S (2016) Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost 14(6):1308–1313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dobesh PP, Fanikos J (2016) Reducing the risk of stroke in patients with nonvalvular atrial fibrillation with direct oral anticoagulants. Is one of these not like the others? J Atr Fibrillation 9(2):1481

    PubMed  PubMed Central  Google Scholar 

  9. Cohen AT, Imfeld S, Rider T (2014) Phase III trials of new oral anticoagulants in the acute treatment and secondary prevention of VTE: comparison and critique of study methodology and results. Adv Ther. 31(5):473–493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Noseworthy PA, Yao X, Abraham NS, Sangaralingham LR, Mcbane RD, Shah ND (2016) Direct comparison of dabigatran, rivaroxaban, and apixaban for effectiveness and safety in nonvalvular atrial fibrillation. Chest 150(6):1302–1312

    Article  PubMed  Google Scholar 

  11. Tittl L, Endig S, Marten S, Reitter A, Beyer-westendorf I, Beyer-westendorf J (2018) Impact of BMI on clinical outcomes of NOAC therapy in daily care—results of the prospective Dresden NOAC Registry (NCT01588119). Int J Cardiol 262:85–91

    Article  CAS  PubMed  Google Scholar 

  12. Kaatz S, Ahmad D, Spyropoulos AC, Schulman S (2015) Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 13:2119–2126

    Article  CAS  PubMed  Google Scholar 

  13. Cunningham A, Stein CM, Chung CP, Daugherty JR, Smalley WE, Ray WA (2011) An automated database case definition for serious bleeding related to oral anticoagulant use. Pharmacoepidemiol Drug Saf 20(6):560–566

    Article  PubMed  PubMed Central  Google Scholar 

  14. Barbar S, Noventa F, Rossetto V et al (2010) A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost 8(11):2450–2457

    Article  CAS  PubMed  Google Scholar 

  15. Ruíz-giménez N, Suárez C, González R et al (2008) Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry. Thromb Haemost 100(1):26–31

    Article  CAS  PubMed  Google Scholar 

  16. Body mass index – BMI. Euro.who.int. http://www.euro.who.int/en/health-topics/disease-prevention/nutrition/a-healthy-lifestyle/body-mass-index-bmi. Accessed September 23, 2018.

  17. Graves KK, Edholm K, Johnson SA (2017) Use of oral anticoagulants in obese patients. JSM Atheroscler. 2(4):1035

    Google Scholar 

  18. Tittl L, Endig S, Marten S, Reitter A, Beyer-westendorf I, Beyer-westendorf J (2018) Impact of BMI on clinical outcomes of NOAC therapy in daily care - Results of the prospective Dresden NOAC Registry (NCT01588119). Int J Cardiol 262:85–91

    Article  CAS  PubMed  Google Scholar 

  19. Lavie CJ, Mcauley PA, Church TS, Milani RV, Blair SN (2014) Obesity and cardiovascular diseases: implications regarding fitness, fatness, and severity in the obesity paradox. J Am Coll Cardiol 63(14):1345–1354

    Article  PubMed  Google Scholar 

  20. Hainer V, Aldhoon-hainerová I (2013) Obesity paradox does exist. Diabetes Care 36(Suppl 2):S276–S281

    Article  PubMed  PubMed Central  Google Scholar 

  21. Hansel B, Roussel R, Elbez Y et al (2015) Cardiovascular risk in relation to body mass index and use of evidence-based preventive medications in patients with or at risk of atherothrombosis. Eur Heart J 36(40):2716–2728

    Article  PubMed  Google Scholar 

  22. Abed HS, Wittert GA (2013) Obesity and atrial fibrillation. Obes Rev 14(11):929–938

    Article  CAS  PubMed  Google Scholar 

  23. Stein PD, Beemath A, Olson RE (2005) Obesity as a risk factor in venous thromboembolism. Am J Med 118(9):978–980

    Article  PubMed  Google Scholar 

  24. Sandhu RK, Ezekowitz J, Andersson U et al (2016) The ‘obesity paradox’ in atrial fibrillation: observations from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Eur Heart J 37(38):2869–2878

    Article  PubMed  Google Scholar 

  25. Balla SR, Cyr DD, Lokhnygina Y et al (2017) Relation of risk of stroke in patients with atrial fibrillation to body mass index (from patients treated with rivaroxaban and warfarin in the rivaroxaban once daily oral direct factor xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation trial). Am J Cardiol 119(12):1989–1996

    Article  CAS  PubMed  Google Scholar 

  26. Schulman S, Kearon C, Kakkar AK et al (2009) Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 361(24):2342–2352

    Article  CAS  PubMed  Google Scholar 

  27. Büller HR, Décousus H, Grosso MA et al (2013) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 369(15):1406–1415

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Sarah Meeks for mentorship & Sarah Ferrell and Christopher Liston for aiding in data collection.

Funding

Dr. William Wilson is a member on the Eliquis® Advisory Board but accepts no financial contributions. No financial support or grants were used to fund this study. All funding was done by Parkview Health.

Author information

Authors and Affiliations

  1. Department of Pharmacy, Parkview Health, 11109 Parkview Plaza Drive, Fort Wayne, IN, 46845, USA

    Jared Netley & Kris Howard

  2. Department of Cardiology, Parkview Health, 11109 Parkview Plaza Drive, Fort Wayne, IN, 46845, USA

    William Wilson

Authors
  1. Jared Netley
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kris Howard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. William Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jared Netley.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Netley, J., Howard, K. & Wilson, W. Effects of body mass index on the safety and effectiveness of direct oral anticoagulants: a retrospective review. J Thromb Thrombolysis 48, 359–365 (2019). https://doi.org/10.1007/s11239-019-01857-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-019-01857-2

Keywords

Search

Navigation