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Effect of Rivaroxaban or Apixaban in Atrial Fibrillation Patients with Stage 4–5 Chronic Kidney Disease or on Dialysis

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Abstract

Background

Anticoagulant treatment in non-valvular atrial fibrillation (AF) patients with severe chronic kidney disease (CKD) or on dialysis remains a matter of debate. The object of this study was to quantify the benefit-risk profiles of rivaroxaban or apixaban versus warfarin in AF patients with stage 4–5 CKD or on dialysis.

Method

A comprehensive search of the Cochrane Library, PubMed, Ovid, and Google Scholar databases was performed for eligible studies that comparing the effect and safety of rivaroxaban or apixaban versus warfarin in AF patients with stage 4–5 CKD or on dialysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were abstracted, and then pooled using a random-effects model.

Results

A total of seven studies, one post hoc analysis of RCT and six observational cohorts, were included in this meta-analysis. Compared with warfarin use, the use of rivaroxaban or apixaban was significantly associated with reduced risks of all-cause death (HR = 0.82, 95% CI 0.72–0.93) and gastrointestinal bleeding (HR = 0.87, 95% CI 0.80–0.95). There were no significant differences in the risks of stroke or systemic embolism (rivaroxaban, HR = 0.71, 95% CI 0.43–1.19; apixaban, HR = 0.86, 95%CI 0.68–1.09) and major bleeding (rivaroxaban, HR = 0.96, 95% CI 0.64–1.45; apixaban, HR = 0.56, 95%CI 0.28–1.12).

Conclusions

Current evidence suggests that rivaroxaban or apixaban are safe and at least as effective as warfarin in patients with AF and stage 4–5 CKD or on dialysis.

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Data Availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Code Availability

Review Manager version 5.3 software (the Cochrane Collaboration 2014, Nordic Cochrane Centre Copenhagen, Denmark), the Stata software (version 15.0, Stata Corp LP, College Station, TX), and MetaXL (version 5.3).

References

  1. Klijn CJ, Paciaroni M, Berge E, et al. Antithrombotic treatment for secondary prevention of stroke and other thromboembolic events in patients with stroke or transient ischemic attack and non-valvular atrial fibrillation: a European stroke organisation guideline. Eur Stroke J. 2019;4(3):198–223.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Heidbuchel H, Verhamme P, Alings M, et al. Updated European heart rhythm association practical guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2015;17(10):1467–507.

    Article  PubMed  Google Scholar 

  3. January CT, Wann LS, Calkins H, et al. 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. 2019;140(2):e125–51.

    Article  PubMed  Google Scholar 

  4. Furie KL, Goldstein LB, Albers GW, et al. Oral antithrombotic agents for the prevention of stroke in nonvalvular atrial fibrillation: a science advisory for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012;43(12):3442–53.

    Article  PubMed  Google Scholar 

  5. Holbrook AM, Pereira JA, Labiris R, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005;165(10):1095–106.

    Article  CAS  PubMed  Google Scholar 

  6. Steffel J, Verhamme P, Potpara TS, et al. The 2018 European heart rhythm association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 2018;39(16):1330–93.

    CAS  PubMed  Google Scholar 

  7. Bansal N, Zelnick LR, Alonso A, et al. eGFR and albuminuria in relation to risk of incident atrial fibrillation: a meta-analysis of the Jackson heart study, the multi-ethnic study of atherosclerosis, and the cardiovascular health study. Clin J Am Soc Nephrol. 2017;12(9):1386–98.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Go AS, Fang MC, Udaltsova N, et al. Impact of proteinuria and glomerular filtration rate on risk of thromboembolism in atrial fibrillation: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study. Circulation. 2009;119(10):1363–9.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Gill S, Jun M, Ravani P. Atrial fibrillation and chronic kidney disease: struggling through thick and thin. Nephrol Dial Transplant. 2017;32(7):1079–84.

    CAS  PubMed  Google Scholar 

  10. Kumar S, Lim E, Covic A, et al. Anticoagulation in concomitant chronic kidney disease and atrial fibrillation: JACC review topic of the week. J Am Coll Cardiol. 2019;74(17):2204–15.

    Article  CAS  PubMed  Google Scholar 

  11. Dahal K, Kunwar S, Rijal J, Schulman P, Stroke LJ, Bleeding M. Mortality outcomes in warfarin users with atrial fibrillation and chronic kidney disease: a meta-analysis of observational studies. Chest. 2016;149(4):951–9.

    Article  PubMed  Google Scholar 

  12. Weber J, Olyaei A, Shatzel J. The efficacy and safety of direct oral anticoagulants in patients with chronic renal insufficiency: a review of the literature. Eur J Haematol. 2019;102(4):312–8.

    Article  CAS  PubMed  Google Scholar 

  13. Hijazi Z, Hohnloser SH, Andersson U, et al. 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. 2016;1(4):451–60.

    Article  PubMed  Google Scholar 

  14. Di Lullo L, Tripepi G, Ronco C, et al. Safety and effectiveness of rivaroxaban and warfarin in moderate-to-advanced CKD: real world data. J Nephrol. 2018;31(5):751–6.

    Article  PubMed  CAS  Google Scholar 

  15. Zhang L, Steckman DA, Adelstein EC, et al. Oral anticoagulation for atrial fibrillation thromboembolism prophylaxis in the chronic kidney disease population: the state of the art in 2019. Cardiovasc Drugs Ther. 2019;33(4):481–8.

    Article  PubMed  Google Scholar 

  16. Stanton BE, Barasch NS, Tellor KB. Comparison of the safety and effectiveness of apixaban versus warfarin in patients with severe renal impairment. Pharmacotherapy. 2017;37(4):412–9.

    Article  CAS  PubMed  Google Scholar 

  17. Higgins J, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. Available at: www.cochrane-handbook.org. Accessed 28 May 2020.

  18. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Randhawa MS, Vishwanath R, Rai MP, et al. Association between use of warfarin for atrial fibrillation and outcomes among patients with end-stage renal disease: a systematic review and meta-analysis. JAMA Netw Open. 2020;3(4):e202175.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kuno T, Takagi H, Ando T, et al. Oral anticoagulation for patients with atrial fibrillation on long-term Dialysis. J Am Coll Cardiol. 2020;75(3):273–85.

    Article  CAS  PubMed  Google Scholar 

  21. van Zyl M, Abdullah HM, Noseworthy PA, Siontis KC. Stroke prophylaxis in patients with atrial fibrillation and end-stage renal disease. J Clin Med. 2020;9(1):123.

    Article  PubMed Central  CAS  Google Scholar 

  22. Ha JT, Neuen BL, Cheng LP, et al. Benefits and harms of oral anticoagulant therapy in chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med. 2019;171(3):181–9.

    Article  PubMed  Google Scholar 

  23. Feldberg J, Patel P, Farrell A, et al. A systematic review of direct oral anticoagulant use in chronic kidney disease and dialysis patients with atrial fibrillation. Nephrol Dial Transplant. 2019;34(2):265–77.

    Article  CAS  PubMed  Google Scholar 

  24. Liu X, Xu Z, Yu P, Yuan P, Zhu W. Non-vitamin K antagonist oral anticoagulants in secondary stroke prevention in atrial fibrillation patients: an updated analysis by adding observational studies. Cardiovasc Drugs Ther. 2020;34(4):569–78.

    Article  PubMed  Google Scholar 

  25. Zhu W, Wan R, Liu F, et al. Relation of body mass index with adverse outcomes among patients with atrial fibrillation: a meta-analysis and systematic review. J Am Heart Assoc. 2016;5(9):e004006.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Bhatia HS, Bailey J, Unlu O, Hoffman K, Kim RJ. Efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation and chronic kidney disease. Pacing Clin Electrophysiol. 2019;42(11):1463–70.

    Article  PubMed  Google Scholar 

  27. Steuber TD, Shiltz DL, Cairns AC, Ding Q, Binger KJ, Courtney JR. A multicenter analysis of factors associated with apixaban-related bleeding in hospitalized patients with end-stage renal disease on hemodialysis. Ann Pharmacother. 2017;51(11):954–60.

    Article  CAS  PubMed  Google Scholar 

  28. Herndon K, Guidry TJ, Wassell K, Elliott W. Characterizing the safety profile of apixaban versus warfarin in moderate to severe chronic kidney disease at a veterans affairs hospital. Ann Pharmacother. 2020;54(6):554–60.

    Article  PubMed  Google Scholar 

  29. Schafer JH, Casey AL, Dupre KA, Staubes BA. Safety and efficacy of apixaban versus warfarin in patients with advanced chronic kidney disease. Ann Pharmacother. 2018;52(11):1078–84.

    Article  CAS  PubMed  Google Scholar 

  30. Reed D, Palkimas S, Hockman R, Abraham S, Le T, Maitland H. Safety and effectiveness of apixaban compared to warfarin in dialysis patients. Res Prac Thrombosis Haemostasis. 2018;2(2):291–8.

    Article  Google Scholar 

  31. Sarratt SC, Nesbit R, Moye R. Safety outcomes of apixaban compared with warfarin in patients with end-stage renal disease. Ann Pharmacother. 2017;51(6):445–50.

    Article  CAS  PubMed  Google Scholar 

  32. De Vriese AS, Caluwé R, Pyfferoen L, et al. Multicenter randomized controlled trial of vitamin K antagonist replacement by rivaroxaban with or without vitamin K2 in hemodialysis patients with atrial fibrillation: the Valkyrie study. J Am Soc Nephrol. 2020;31(1):186–96.

    Article  PubMed  Google Scholar 

  33. Stanifer JW, Pokorney SD, Chertow GM, et al. Apixaban versus warfarin in patients with atrial fibrillation and advanced chronic kidney disease. Circulation. 2020;141(17):1384–92.

    Article  CAS  PubMed  Google Scholar 

  34. Weir MR, Ashton V, Moore KT, Shrivastava S, Peterson ED, Ammann EM. Rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and stage IV-V chronic kidney disease. Am Heart J. 2020;223:3–11.

    Article  CAS  PubMed  Google Scholar 

  35. Makani A, Saba S, Jain SK, et al. Safety and efficacy of direct oral anticoagulants versus warfarin in patients with chronic kidney disease and atrial fibrillation. Am J Cardiol. 2020;125(2):210–4.

    Article  CAS  PubMed  Google Scholar 

  36. Siontis KC, Zhang X, Eckard A, et al. Outcomes associated with apixaban use in patients with end-stage kidney disease and atrial fibrillation in the United States. Circulation. 2018;138(15):1519–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Chan KE, Edelman ER, Wenger JB, Thadhani RI, Maddux FW. Dabigatran and rivaroxaban use in atrial fibrillation patients on hemodialysis. Circulation. 2015;131(11):972–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chang SH, Wu CCV, Yeh YH, et al. Efficacy and safety of oral anticoagulants in patients with atrial fibrillation and stages 4 or 5 chronic kidney disease. Am J Med. 2019;132(11):1335–43.

    Article  CAS  PubMed  Google Scholar 

  39. Coleman CI, Kreutz R, Sood NA, et al. Rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and severe kidney disease or undergoing hemodialysis. Am J Med. 2019;132(9):1078–83.

    Article  CAS  PubMed  Google Scholar 

  40. Andò G, Capranzano P. Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients with chronic kidney disease: a systematic review and network meta-analysis. Int J Cardiol. 2017;231:162–9.

    Article  PubMed  Google Scholar 

  41. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955–62.

    Article  CAS  PubMed  Google Scholar 

  42. Kimachi M, Furukawa TA, Kimachi K, Goto Y, Fukuma S, Fukuhara S. Direct oral anticoagulants versus warfarin for preventing stroke and systemic embolic events among atrial fibrillation patients with chronic kidney disease. Cochrane Database Syst Rev. 2017;11(11):CD011373.

    PubMed  Google Scholar 

  43. Bonde AN, Lip GY, Kamper AL, et al. Net clinical benefit of antithrombotic therapy in patients with atrial fibrillation and chronic kidney disease: a nationwide observational cohort study. J Am Coll Cardiol. 2014;64(23):2471–82.

    Article  CAS  PubMed  Google Scholar 

  44. Oliver T, Salman LA, Ciaudelli B, Cohen DA. Anticoagulation-related nephropathy: the most common diagnosis you've never heard of. Am J Med. 2019;132(8):e631–3.

    Article  PubMed  Google Scholar 

  45. Dreisbach AW, Japa S, Gebrekal AB, et al. Cytochrome P4502C9 activity in end-stage renal disease. Clin Pharmacol Ther. 2003;73(5):475–7.

    Article  CAS  PubMed  Google Scholar 

  46. Yao X, Tangri N, Gersh BJ, Shah ND, Nath KA, Noseworthy PA. Renal outcomes in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol. 2017;70(21):2621–32.

    Article  PubMed  Google Scholar 

  47. Fordyce CB, Hellkamp AS, Lokhnygina Y, et al. On-treatment outcomes in patients with worsening renal function with rivaroxaban compared with warfarin: insights from ROCKET AF. Circulation. 2016;134(1):37–47.

    Article  CAS  PubMed  Google Scholar 

  48. Hijazi Z, Hohnloser SH, Oldgren J, et al. Efficacy and safety of dabigatran compared with warfarin in patients with atrial fibrillation in relation to renal function over time-a RE-LY trial analysis. Am Heart J. 2018;198:169–77.

    Article  CAS  PubMed  Google Scholar 

  49. Bohula EA, Giugliano RP, Ruff CT, et al. Impact of renal function on outcomes with edoxaban in the ENGAGE AF-TIMI 48 trial. Circulation. 2016;134(1):24–36.

    Article  CAS  PubMed  Google Scholar 

  50. Hohnloser SH, Hijazi Z, Thomas L, et al. Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J. 2012;33(22):2821–30.

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was funded by the National Natural Science Foundation of China (81770392, 81770394, 81700344, 81800344, 81800345), Science and Technology Program Foundation of Guangzhou (201707010124), Guangdong Natural Science Foundation (2017A030310311, 2017A030313795), Young Teachers’ Basic Scientific Research Business Expenses Project (20ykpy72), Medical Research Foundation of Guangdong Province (A2017030, A2018107, A2018082), and China Postdoctoral Science Foundation (2019 M663312, 2019TQ0380, 2019 M660229).

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Contributions

CL and WZ developed the idea of the study. CC obtained the data and wrote the manuscript, YC performed analysis and interpreted the results. YZ participated in data analysis and results interpretation. JM and YD participated in manuscript writing and revision. All authors have read and approved the manuscript and agreed with their contributions.

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Correspondence to Wengen Zhu or Chen Liu.

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Chen, C., Cao, Y., Zheng, Y. et al. Effect of Rivaroxaban or Apixaban in Atrial Fibrillation Patients with Stage 4–5 Chronic Kidney Disease or on Dialysis. Cardiovasc Drugs Ther 35, 273–281 (2021). https://doi.org/10.1007/s10557-021-07144-8

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