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Safety analysis of apixaban versus warfarin in patients with advanced kidney disease

  • Michael Bowie
  • Violet Valencia
  • Ingrid Perez-Alvarez
  • Minh-Ha Tran
Article
  • 142 Downloads

Abstract

Anticoagulation in patients with advanced kidney disease, defined as those with an eGFR < 25 mL/min, including patients with end-stage renal disease on hemodialysis, remains an area of controversy and debate. Due to safety concerns regarding the increased risk for bleeding in this population, these patients have been excluded from all large-scale, randomized controlled trials to date. Warfarin and apixaban are both FDA-approved for use in this population and although warfarin remains the anticoagulant of choice, apixaban use is steadily increasing. This review combines relevant literature to better understand the risk versus benefit of anticoagulation in patients with severe kidney disease as well as the safety of apixaban versus warfarin in this population. High rates of bleed were found among both anticoagulants in those with severe kidney disease, suggesting that the risk for bleed associated with anticoagulation may not outweigh the benefit of treatment. Apixaban was found to be superior in rates of major bleed in those with ESRD on HD and may be superior to warfarin in those with an eGFR < 25 mL/min. However, large-scale, randomized clinical trials are needed to validate these results. With the continued development of novel agents there may be superior alternatives to apixaban and warfarin in those with severe kidney disease in the future.

Keywords

Apixaban Warfarin Anticoagulation Renal insufficiency End-stage renal disease Hemodialysis 

References

  1. 1.
    Bansal V, Herzog C, Sarnak M et al (2017) Oral anticoagulants to prevent stroke in nonvavular atrial fibrillation in patients with CKD stage 5D: an NFK-KDOQI controversies report. Am J Kidney Dis 70(6):859–868.  https://doi.org/10.1053/j.ajkd.2017.08.003 CrossRefPubMedGoogle Scholar
  2. 2.
    Brancacccio D, Neri L, Bellocchio F, Barbieri C et al (2016) Atrial fibrillation in dialysis patients: time to abandon warfarin? Int J Artif Organs 39(3):99–105.  https://doi.org/10.5301/ijao.5000487 CrossRefGoogle Scholar
  3. 3.
    Chan N, Bhagirath V, Eikelboom J (2015) Profile of betrixaban and its potential in the prevention and treatment of venous thromboembolism. Vasc Health Risk Manag 11:343–351.  https://doi.org/10.2147/VHRM.S63060 PubMedPubMedCentralGoogle Scholar
  4. 4.
    Chan K, Guigliano R, Patel M, Abramson S et al (2016) Nonvitamin K anticoagulant agents in patients with advanced chronic kidney disease or on dialysis with AF. J Am Coll Cardiol 67(24):2888–2899.  https://doi.org/10.1016/j.acc.2016.02.082 CrossRefPubMedGoogle Scholar
  5. 5.
    Chang M, Yu Z, Shenker A, Wang J, Pursley J et al (2015) Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of apixaban. J Clin Pharmacol 56(5):637–645.  https://doi.org/10.1002/jcph.633 CrossRefPubMedGoogle Scholar
  6. 6.
    Conway S, Hwang A, Ponte C, Gums J (2017) Laboratory and clinical monitoring of direct oral anticoagulants: what clinicians need to know. Pharmacotherapy 37(2):236–248.  https://doi.org/10.1002/phar.1884 CrossRefPubMedGoogle Scholar
  7. 7.
    Fanikos J, Burnett A, Mahan C, Dobesh P (2017) Renal function considerations for stroke prevention in atrial fibrillation. Am J Med 130(9):1015–1023.  https://doi.org/10.1016/j.amjmed.2017.04.015 CrossRefPubMedGoogle Scholar
  8. 8.
    Granger C, Alexander J, McMurray J et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. New Engl J Med 365:981–992.  https://doi.org/10.1056/NEJMoa1107039 CrossRefPubMedGoogle Scholar
  9. 9.
    Harel Z, Chertow G, Shah P, Harel S, Dorian P, Yan A, Saposnik G et al (2017) Warfarin and the risk of stroke and bleeding in patients with atrial fibrillation receiving dialysis: a systematic review and meta-analysis. Can J Cardiol 33:737–746CrossRefPubMedGoogle Scholar
  10. 10.
    Harel Z, Sood M, Perl J (2015) Comparison of novel oral anticoagulants versus vitamin K antagonists in patients with chronic kidney disease. Curr Opin Nephrol Hypertens 24:183–192.  https://doi.org/10.1097/MNH.0000000000000098 CrossRefPubMedGoogle Scholar
  11. 11.
    Ikeda K, Tachibana H (2015) Clinical implication of monitoring rivaroxaban and apixaban by using anti-factor Xa assay in patients with non-valvular atrial fibrillation. J Arrhythmia 32:42–50CrossRefGoogle Scholar
  12. 12.
    King B, el-Azhary R, McEvoy M et al (2017) Direct oral anticoagulant medications in calciphylaxis. Int J Dermatol 56:1065–1070CrossRefPubMedGoogle Scholar
  13. 13.
    Kufel W, Zayac A, Lehmann D et al (2016) Clinical application and pharmacodynamic monitoring of apixaban in a patient with end-stage renal disease requiring chronic hemodialysis. Pharmacotherapy 36(11):66–71.  https://doi.org/10.1002/phar.1836 CrossRefGoogle Scholar
  14. 14.
    Mavrakanas T, Samer C, Nessim S et al (2017) Apixaban pharmacokinetics at steady state in hemodialysis patients. J Am Soc Nephrol 28:2241–2248.  https://doi.org/10.1681/ASN.2016090980 CrossRefPubMedGoogle Scholar
  15. 15.
    Pathak R, Pandit A, Karmacharya P et al (2015) Meta-analysis on risk of bleeding with apixaban in patients with renal impairment. Am J Cardiol 115(3):323–327.  https://doi.org/10.1016/j.amjcard.2014.10.042 CrossRefPubMedGoogle Scholar
  16. 16.
    Pelliccia F, Rosanio S, Marazzi G et al (2016) Efficacy and safety of novel anticoagulants versus vitamin K antagonists in patients with mild and moderate to severe renal insufficiency: focus on apixaban. Int J Cardiol 225:77–81.  https://doi.org/10.1016/jijcard.2016.09.129 CrossRefPubMedGoogle Scholar
  17. 17.
    Reed D, Palkimas S, Hockman R, Abraham S, Le T, Maitland H (2017) Safety and effectiveness of apixaban compared to warfarin in dialysis patients. Res Pract Thromb Haemost 2:291–298.  https://doi.org/10.1002/rth2.12083 CrossRefGoogle Scholar
  18. 18.
    Sarratt S, Nesbit R, Moye R (2017) Safety outcomes of apixaban compared with warfarin in patients with end-stage renal disease. Ann Pharmacother 51(6):445–450.  https://doi.org/10.1177/1060028017694654 CrossRefPubMedGoogle Scholar
  19. 19.
    Skelley J, Thomason A, Nolen J (2018) Betrixaban (Bevyxxa) A direct-acting oral anticoagulant factor Xa inhibitor. Pharm Ther 43(2):85–88Google Scholar
  20. 20.
    Stanton B, Barasch N, Tellor K (2017) Comparison of the safety and effectiveness of apixaban versus warfarin in patients with severe renal impairment. Pharmacother Publ 37(4):412–419.  https://doi.org/10.1002/phar.1905 CrossRefGoogle Scholar
  21. 21.
    Steuber T, Shiltz D, Cairns A, Ding Q, Binger K, Courtney J (2017) A multicenter analysis of factors associated with apixaban-related bleeding in hospitalized patients with end-stage renal disease of hemodialysis. Ann Pharmacother 51(11):954–960.  https://doi.org/10.1177/1060028017717282 CrossRefPubMedGoogle Scholar
  22. 22.
    Wang X, Tirucherai G, Marbury T et al (2016) Pharmacokinetics, pharmacodynamics, and safety of apixaban in subjects with end-stage renal disease on hemodialysis. J Clin Pharmacol 56(5):628–636.  https://doi.org/10.1002/jcph.628 CrossRefPubMedGoogle Scholar
  23. 23.
    Wendte J, Voss G, VanOverschelde B (2016) Influence of apixaban on antifactor Xa levels in a patient with acute kidney injury. Am J Health-Syst Pharm 73:563–567.  https://doi.org/10.2146/ajhp150360 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Michael Bowie
    • 1
  • Violet Valencia
    • 2
  • Ingrid Perez-Alvarez
    • 3
  • Minh-Ha Tran
    • 3
  1. 1.Department of Internal Medicine-PediatricsLoma Linda University Medical CenterLoma LindaUSA
  2. 2.Department of PharmacyChildren’s Hospital of Orange CountyOrangeUSA
  3. 3.Department of Pathology and Laboratory MedicineUniversity of California, Irvine Medical CenterOrangeUSA

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