Skip to main content
SpringerLink
Log in

Effectiveness and safety of direct oral anticoagulants in patients with venous thromboembolism and creatinine clearance < 30 mL/min

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

Abstract

The few studies that compared direct oral anticoagulants (DOAC) vs. warfarin in the setting of advanced renal insufficiency have focused on patients with atrial fibrillation. The purpose of this observational, matched, cohort study of patients was to assess the effectiveness and safety of DOAC vs. warfarin for the treatment of venous thromboembolism (VTE) among patients with a creatinine clearance (CrCl) < 30 mL/min. This observational, cohort study included patients with VTE and CrCl < 30 mL/min who were newly initiated on a DOAC or warfarin between January 1, 2016 and December 31, 2020. DOAC patients were matched up to 1:2 to warfarin patients. Primary outcome was a composite of recurrent VTE, clinically-relevant bleeding, ischemic stroke, and all-cause mortality. Adjusted conditional, multivariate Cox proportional hazards modeling was used to assess outcomes. 626 DOAC patients were matched to 1071 warfarin patients. DOAC patients had a higher mean age, higher mean baseline CrCl, and were less likely to have been receiving dialysis. There was no statistically significant difference in the composite outcome between groups (adjusted hazard ratio [aHR] 1.13, 95% confidence interval [CI] 0.87–1.47) or in the individual components of the composite (all HR 95% CI crossed 1.00). Identification of statistically non-significant rates of bleeding and thromboembolic outcomes suggest that the use of DOAC or warfarin is reasonable in patients with VTE and CrCl < 30 mL/min.

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
Fig. 2

Similar content being viewed by others

Data availability

Preliminary data were presented by pharmacy residents at the American Society of Health-System Pharmacists Midyear Clinical Meeting and Exhibition, Las Vegas, NV, on December 8, 2021; Southeastern Residency Conference, Athens, GA, on April 21, 2022; Eastern States Conference for Pharmacy Residents and Preceptors, Virtual, on May 12, 2022; Western States Conference, San Diego, CA, on May 17, 2022; Oregon Society of Health System Pharmacists Northwestern States Residency Conference, Virtual, on May 20, 2022; Residency Conference of the Rockies, Estes Park, CO, on June 1, 2022; and San Fernando Valley Chapter Continuing Pharmacy Education: Pharmacy Resident Research Education Session, Virtual, on June 13, 2022.

References

  1. Centers for Disease Control and Prevention (2021) Chronic kidney disease in the United States, 2021. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention. https://www.cdc.gov/kidneydisease/pdf/Chronic-Kidney-Disease-in-the-US-2021-h.pdf. Accessed 31 Oct 2022

  2. Facts about Chronic Kidney Disease (2017) National kidney foundation. www.kidney.org/atoz/content/about-chronic-kidney-disease. Accessed 31 Oct 2022

  3. Magnocavallo M, Bellasi A, Mariani MV et al (2020) Thromboembolic and bleeding risk in atrial fibrillation patients with chronic kidney disease: role of anticoagulation therapy. J Clin Med 10:83

    Article  PubMed  PubMed Central  Google Scholar 

  4. January CT, Wann LS, Calkins H et al (2019) 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. Circulation 140:e125–e151

    Article  PubMed  Google Scholar 

  5. Hijazi Z, Hohnloser SH, Andersson U et al (2016) Efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation in relation to renal function over time: insights from the ARISTOTLE randomized clinical trial. JAMA Cardiol 1:451–460

    Article  PubMed  Google Scholar 

  6. Fox KA, Piccini JP, Wojdyla D et al (2011) Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment. Eur Heart J 32:2387–2394

    Article  CAS  PubMed  Google Scholar 

  7. Hijazi Z, Hohnloser SH, Oldgren J et al (2014) Efficacy and safety of dabigatran compared with warfarin in relation to baseline renal function in patients with atrial fibrillation: a RE-LY (Randomized evaluation of long-term anticoagulation therapy) trial analysis. Circulation 129:961–970

    Article  CAS  PubMed  Google Scholar 

  8. Harel Z, Sholzberg M, Shah PS et al (2019) Comparisons between novel oral anticoagulants and vitamin K antagonists in patients with CKD. J Am Soc Nephrol 25:431–442

    Article  Google Scholar 

  9. Aursulesei V, Costache II (2019) Anticoagulation in chronic kidney disease: from guidelines to clinical practice. Clin Cardiol 42:774–782

    Article  PubMed  PubMed Central  Google Scholar 

  10. Chang M, Yu Z, Shenker A et al (2016) Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of apixaban. J Clin Pharmacol 56:637–645

    Article  CAS  PubMed  Google Scholar 

  11. Kubitza D, Becka M, Mueck W al (2010) Effects of renal impairment on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban, an oral, direct factor xa inhibitor. Br J Clin Pharmacol 70:703–712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Stangier J, Rathgen K, Stähle H, Mazur D (2010) Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet 49:259–268

    Article  CAS  PubMed  Google Scholar 

  13. Winter MA, Guhr KN, Berg GM (2012) Impact of various body weights on serum creatinine concentrations on the bias and accuracy of the Cockcroft-Gault equation. Pharmacotherapy 32:604–612

    Article  CAS  PubMed  Google Scholar 

  14. Kaatz S, Ahmad D, Spyropoulos AC, Schulman S, for the Subcommittee on Control of Anticoagulation (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 

  15. Hall R, Mondor L, Porter J, Fang J, Kapral MK (2016) Accuracy of administrative data for the coding of acute stroke and TIAs. Can J Neurol Sci 43:765–773

    Article  PubMed  Google Scholar 

  16. Clark DO, Von KM, Saunders K, Baluch WM, Simon GE (1995) A chronic disease score with empirically derived weights. Med Care 33:783–795

    Article  CAS  PubMed  Google Scholar 

  17. Quan H, Sundararajan V, Halfon P et al (2005) Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 3:1130–1139

    Article  Google Scholar 

  18. Bergstralh EJ, Kosanke JL(1995) Computerized matching of controls. Section of biostatistics technical report number 56. Mayo Foundation. https://www.mayo.edu/research/documents/biostat-56pdf/doc-10026923. Accessed 31 October 2022

  19. Alhousani M, Malik SU, Abu-Hashyeh A et al (2021) Using oral anticoagulants among chronic kidney disease patients to prevent recurrent venous thromboembolism: a systematic review and meta-analysis. Thromb Res 198:103–114

    Article  CAS  PubMed  Google Scholar 

  20. Cohen AT, Sah J, Dhamane AD et al (2022) Effectiveness and safety of apixaban versus warfarin in venous thromboembolism patients with chronic kidney disease. Thromb Haemost 122:926–938

    Article  PubMed  Google Scholar 

  21. Hanni C, Petrovitch E, Ali M et al (2020) Outcomes associated with apixaban vs warfarin in patients with renal dysfunction. Blood Adv 4:2366–2371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Reed D, Palkimas S, Hockman R, Abraham S, Le T, Maitland H (2018) Safety and effectiveness of apixaban compared to warfarin in dialysis patients. Res Pract Thromb Haemost 2:291–298

    Article  PubMed  PubMed Central  Google Scholar 

  23. Sarratt SC, Nesbit R, Moye R (2017) Safety outcomes of apixaban compared with warfarin in patients with end-stage renal disease. Ann Pharmacother 51:445–450

    Article  CAS  PubMed  Google Scholar 

  24. Schafer JH, Casey AL, Dupre KA, Staubes BA (2018) Safety and efficacy of apixaban versus warfarin in patients with advanced chronic kidney disease. Ann Pharmacother 52:1078–1084

    Article  CAS  PubMed  Google Scholar 

  25. Stanton BE, Barasch NS, Tellor KB (2017) Comparison of the safety and effectiveness of apixaban versus warfarin in patients with severe renal impairment. Pharmacotherapy 37:412–419

    Article  CAS  PubMed  Google Scholar 

  26. Millar CM, Laffan MA (2017) Drug therapy in anticoagulation: which drug for which patient? Clin Med 17:233–244

    Article  Google Scholar 

  27. Chan KE, Edelman ER, Wenger JB, Thadhani RI, Maddux FW (2015) Dabigatran and rivaroxaban use in atrial fibrillation patients on hemodialysis. Circulation 131:972–979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Joos C, Lawrence K, Jones AE, Johnson SA, Witt DM (2019) Accuracy of ICD-10 codes for identifying hospitalizations for acute anticoagulation therapy-related bleeding events. Thromb Res 181:71–76

    Article  CAS  PubMed  Google Scholar 

  29. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2013) KDIGO clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3:1–150

    Google Scholar 

Download references

Funding

Funding was provided by Kaiser Permanente. This research did not receive any specific Grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Pharmacy Department, University of Maryland St. Joseph Medical Center, Towson, MD, USA

    Lauren Cline

  2. Pharmacy Department, Kaiser Permanente Southern California, Woodland Hills, CA, USA

    Erika Marie G. Generoso, Kimi Pontoppidan & Hasmig Ekmekdjian

  3. Pharmacy Department, Boston Medical Center, Boston, MA, USA

    Nicholas D’Apice

  4. Pharmacy Department, Kaiser Permanente Georgia, Atlanta, GA, USA

    Sara K. Dellinger & Stephanie A. Hale

  5. Pharmacy Department, Kaiser Permanente Northwest, Portland, OR, USA

    Amber Tovey & Tanya Ramsey

  6. Pharmacy Department, Kaiser Permanente Colorado, Aurora, CO, USA

    Nathan P. Clark

  7. Pharmacy Outcomes Research Group, Kaiser Permanente National Pharmacy, Downey, CA, USA

    Fang Nui

  8. Pharmacy Outcomes Research Group, Kaiser Permanente National Pharmacy, Oakland, CA, USA

    Rita Hui

  9. Pharmacy Department, Kaiser Permanente Mid-Atlantic States, Hyattsville, MD, USA

    Kristen Fink

  10. College of Pharmacy, University of Utah, Salt Lake City, UT, USA

    Daniel M. Witt

  11. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada

    Mark A. Crowther

  12. Pharmacy Outcomes Research Group, Kaiser Permanente National Pharmacy, 16601 E. Centretech Pkwy, Aurora, CO, 80011, USA

    Thomas Delate

Authors
  1. Lauren Cline
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erika Marie G. Generoso
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicholas D’Apice
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sara K. Dellinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Amber Tovey
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nathan P. Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fang Nui
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rita Hui
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Stephanie A. Hale
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tanya Ramsey
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kimi Pontoppidan
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Hasmig Ekmekdjian
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Kristen Fink
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Daniel M. Witt
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Mark A. Crowther
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Thomas Delate
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

LC, ND, SD, EG, AT, NC, FN, RH, SH, TR, KP, HE, KF, DW, MC, and TD designed the research, interpreted the analysis, and revised the manuscript; TD extracted information from electronic data sources and performed the statistical analysis; LC, ND, SD, EG, AT, and RH performed manual chart reviews to validate outcomes; LC, ND, SD, EG, and AT drafted the initial version of the manuscript; and LC, ND, SD, EG, AT, NC, FN, RH, SH, TR, KP, HE, KF, DW, MC, and TD approved the version of the manuscript for submission. LC, ND, SD, EG, and AT contributions to the research occurred while Kaiser Permanente pharmacy residents.

Corresponding author

Correspondence to Thomas Delate.

Ethics declarations

Conflict of Interest

All authors declare no conflict of interest regarding the present work, and they have no involvements that might raise the question of bias in the work reported or in the conclusions, implications, or opinions stated. No authors have financial or non-financial interests that are directly or indirectly related to the work submitted for publication.

Additional information

Publisher’s Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cline, L., Generoso, E.M.G., D’Apice, N. et al. Effectiveness and safety of direct oral anticoagulants in patients with venous thromboembolism and creatinine clearance < 30 mL/min. J Thromb Thrombolysis 55, 355–364 (2023). https://doi.org/10.1007/s11239-022-02758-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-022-02758-7

Keywords

Search

Navigation