Skip to main content

Effectiveness and safety of rivaroxaban versus warfarin in obese patients with acute venous thromboembolism: analysis of electronic health record data

Abstract

There is limited data evaluating clinical outcomes of rivaroxaban versus warfarin in obese patients with venous thromboembolism (VTE). Our objective was to evaluate the effectiveness and safety of rivaroxaban versus warfarin in obese VTE patients. We performed a cohort analysis using Optum® De-Identified Electronic Health Record data from 11/1/2012 to 9/30/2018. Patients with a body mass index (BMI) ≥ 30 kg/m2 admitted to the hospital, emergency department or observation unit for VTE, prescribed rivaroxaban or warfarin as their first oral anticoagulant (OAC) within 7-days and had ≥12-months of EHR activity prior were included. We excluded patients with OAC use at baseline or cancer. Patients were 1:1 matched (standard differences<0.10). Primary outcomes were recurrent VTE and major bleeding at 3-, 6- and 12-months using an intent-to-treat approach. Subanalyses of BMI 30.0–34.9, 35.0–39.9 and ≥ 40 kg/m2 were performed. Risk was compared using Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CI). We identified 6755 rivaroxaban and 6755 warfarin users with BMI ≥ 30 kg/m2 and incident VTE. At 3-, 6- and 12-months, rivaroxaban was associated with a reduced hazard of recurrent VTE compared to warfarin (HR 0.61, 95%CI   0.51–0.72; HR 0.65, 95%CI  0.55–0.77; HR 0.63, 95%CI  0.54–0.74) with no difference in major bleeding (HR  0.99, 95%CI  0.68–1.44; HR 0.90, 95%CI  0.64–1.26; HR 1.00, 95%CI  0.73–1.36). No statistical difference was found across BMI categories for either recurrent VTE (p-interaction≥0.43) or major bleeding (p-interaction ≥ 0.58) at any time point. In obese VTE patients, prescription of rivaroxaban was associated with a significantly reduced risk of recurrent VTE versus warfarin, without impacting major bleeding. Our findings remained consistent across BMI classes.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Data availability

Data used in this study were obtained from Optum® under a license to Janssen Pharmaceuticals (and provided to Dr. Coleman under a third-party agreement) and are not publicly available.

References

  1. January CT, Wann LS, Calkin H et al (2019) AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the Heart Rhythm Society in collaboration with the Society of Thoracic Surgeons. J Am Coll Cardiol 9:104–132

    Article  Google Scholar 

  2. Stein PD, Beemath A, Olson RE (2015) Obesity as a risk factor in venous thromboembolism. Am J Med 118:978–980

    Article  Google Scholar 

  3. Hanley MJ, Abernethy DR, Greenblatt DJ et al (2010) Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet 29:71–87

    Article  Google Scholar 

  4. Kubitza D, Becka M, Zuehlsdorf M et al (2007) Body weight has limited influence on the safety, tolerability, pharmacokinetics, or pharmacodynamics of rivaroxaban (BAY 59-7939) in healthy subjects. J Clin Pharmacol 47:218–226

    CAS  Article  Google Scholar 

  5. Di Nisio M, Vedovati MC, Riera-Mestre A et al (2016) Treatment of venous thromboembolism with rivaroxaban in relation to body weight. A sub-analysis of the EINSTEIN DVT/PE studies. Thromb Haemost 116:739–746

    Article  Google Scholar 

  6. Spyropoulos AC, Ashton V, Chen YW et al (2019) Rivaroxaban versus warfarin treatment among morbidly obese patients with venous thromboembolism: comparative effectiveness, safety, and costs. Thromb Res 182:159–166

    CAS  Article  Google Scholar 

  7. Kalani C, Awudi E, Alexander T et al (2019) Evaluation of the efficacy of direct oral anticoagulants (DOACs) in comparison to warfarin in morbidly obese patient. Hosp Pract 47:181–185

    Article  Google Scholar 

  8. Tittl L, Ending S, Marten S (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

    CAS  Article  Google Scholar 

  9. Kushnir M, Choi Y, Eisenberg R et al (2019) Efficacy and safety of direct oral factor Xa inhibitors compared with warfarin patients with morbid obesity: a single-Centre retrospective analysis of chart data. Lancet. 6:e359–e365

    Google Scholar 

  10. Martin BJ, Chen G, Graham M et al (2014) Coding of obesity in administrative hospital discharge abstract data: accuracy and impact for future research studies. BMC Health Serv Res 14:70

    Article  Google Scholar 

  11. Lloyd JR, Blackwell SA, Wei II et al (2015) Validity of a claims-based diagnosis of obesity among Medicare beneficiaries. Eval Health Prof 28:508–517

    Article  Google Scholar 

  12. Ammann EM, Kalsekar I, Yoo A et al (2018) Validation of body mass index (BMI)-related ICD-9-CM and ICD-10-CM administrative diagnosis codes recorded in US claims data. Pharmacoepidemiol Drug Saf 27:1092–1100

    Article  Google Scholar 

  13. Jain R, Watzker A, Luo X et al (2020) Validation of obesity coding among newly treated nonvalvular atrial fibrillation patient using an integrated electronic medical record and claims database. Curr Med Res Opin 36:189–197

    Article  Google Scholar 

  14. Optum (2018) Optum EHR offering. Optum Inc, https://www.optum.com/campaign/ls/data-new-era-of-visibility/download.html. Accessed 28 July 2019

  15. Benchimol EI, Smeeth L, Guttmann A et al (2015) RECORD working committee. The REporting of studies conducted using observational routinely-collected health data (RECORD) statement. PLoS Med 12:e1001885

    Article  Google Scholar 

  16. White RH, Garcia M, Sadeghi B et al (2010) Evaluation of the predictive value of ICD-9-CM coded administrative data for venous thromboembolism in the United States. Thromb Res 126:61–67

    CAS  Article  Google Scholar 

  17. National Heart, Lung and Blood Institute. Classification of overweight and obesity by BMI, waist circumference, and associated disease risks. https://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmi_dis.htm. Accessed 25 Sept 2019

  18. Austin PC (2011) An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivar Behav Res 46:399–424

    Article  Google Scholar 

  19. Cunningham A, Stein CM, Chung CP et al (2011) An automated database case definition for serious bleeding related to oral anticoagulant use. Pharmacoepidemiol Drug Saf 20:560–566

    Article  Google Scholar 

  20. Altman DG, Bland JM (2003) Interaction revisited: the difference between two estimates. BMJ 326:219

    Article  Google Scholar 

  21. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B 57:289–300

    Google Scholar 

  22. Rivaroxaban package insert. Titusville, NJ: Janssen Pharmaceuticals; 2016 May

  23. Gong X, Wang H, Yuan Y (2016) Analysis of the first therapeutic-target-achieving time of warfarin therapy and associated factors in patients with pulmonary embolism. Exp Ther Med 12:2265–2274

    Article  Google Scholar 

  24. Wallace JL, Reaves AB, Tolley EA et al (2013) Comparison of initial warfarin response in obese patients versus non-obese patients. J Thromb Thrombolysis 1:96–101

    Article  Google Scholar 

  25. Erkens PM, ten Cate H, Büller HR, Prins MH (2012) Benchmark for time in therapeutic range in venous thromboembolism: a systematic review and meta-analysis. PLoS ONE 7:e42269

    CAS  Article  Google Scholar 

  26. Gandhi SK, Salmon W, Kong SX, Zhao SZ (1999) Administrative databases and outcomes assessment: an overview of issues and potential utility. J Manag Care Spec Pharm 5:215–222

    Google Scholar 

  27. CMS Chronic Conditions Major Warehouse. https://www2.ccwdata.org/web/guest/home/. Accessed 1 Apr 2020

  28. Elixhauser A, Steiner C, Harris DR et al (1998) Comorbidity measures for use with administrative data. Med Care 36(1):8–27

    CAS  Article  Google Scholar 

  29. Dentali F, Gessi V, Marucci R et al (2017) Lipoprotein(a) as a risk factor for venous thromboembolism: a systematic review and meta-analysis of the literature. Semin Thromb Hemost 43:614–620

    CAS  Article  Google Scholar 

  30. Francesco Z, Kunutsor S, Seidu S et al (2018) Is the lower risk of venous thromboembolism with statins relaed to low-density-lipoprotein reduction? A network meta-analysis and meta-regression of randomized controlled trials. Atherosclerosis 271:223–231

    Article  Google Scholar 

  31. Kunutsor SK, Seidu S, Khunti K (2017) Statins and secondary prevention of venous thromboembolism: pooled analysis of published observational cohort sutides. Eur Heart J 38:1608–1612

    Article  Google Scholar 

Download references

Funding

This study was funded by Janssen Scientific Affairs, LLC, Titusville, NJ, USA.

Author information

Authors and Affiliations

Authors

Contributions

OSC, CIC, JBW, VA, DM and KTM conceptualized and designed the study. OSC, CIC and TJB analyzed the data. Data interpretation was done by all authors. The manuscript was written primarily by OSC and CIC; all authors contributed to revisions. All authors substantially contributed to this project, read and approved the manuscript and assume responsibility for the contents of the manuscript.

Corresponding author

Correspondence to Craig I. Coleman.

Ethics declarations

Conflict of interest

C. I. Coleman has received grant funding and consultancy fees from Janssen Scientific Affairs LLC, Titusville, NJ, Bayer AG, Berlin, Germany; Portola Pharmaceuticals, South San Francisco, CA; and speaker fees from Medscape Inc. J. Beyer-Westendorf has grant funding and consultancy fees from Bayer AG, Berlin, Germany; Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT; Pfizer New York, NY; Daiichi Sankyo, Basking Ridge, NJ; and Portola Pharmaceuticals, South San Francisco, CA. V. Ashton and D. Milentijevic are employees of Janssen Scientific Affairs LLC, Titusville, NJ. KT. Moore is an employee of Janssen Pharmaceuticals Inc., Titusville, NJ. O. S. Costa and T. J. Bunz have no declarations-of-interest.

Additional information

Publisher's Note

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

Electronic supplementary material

Below is the link to the electronic supplementary material.

Electronic supplementary material 1 (DOCX 70 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Costa, O.S., Beyer-Westendorf, J., Ashton, V. et al. Effectiveness and safety of rivaroxaban versus warfarin in obese patients with acute venous thromboembolism: analysis of electronic health record data. J Thromb Thrombolysis 51, 349–358 (2021). https://doi.org/10.1007/s11239-020-02199-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-020-02199-0

Keywords

  • Anticoagulants
  • Rivaroxaban
  • Warfarin
  • Obesity
  • Venous thromboembolism