Original Article

CME Article: Safety of Nonvitamin K Antagonists Compared with Warfarin in Patients with Atrial Fibrillation and End-Stage Kidney Disease

Authors: Nathan A. Pinner, PharmD, Alyssa J. Osmonson, PharmD, Jessica A. Starr, PharmD

Abstract

Objectives: This study evaluated the occurrence of major bleeding following the initiation of oral anticoagulation therapy in patients with end-stage kidney disease (ESKD) in a community teaching hospital.

Methods: This was a single-center retrospective study that enrolled patients admitted to the study hospital with ESKD and who received oral anticoagulation (warfarin or nonvitamin K oral antagonists [NOACs]). The primary endpoint was the occurrence of major bleeding at any time while taking oral anticoagulation. Key secondary endpoints included occurrence of minor bleeding, thrombotic events, and hospitalizations because of bleeding or thrombosis.

Results: There were 36 patients who received warfarin and 32 patients who received a NOAC. A major bleeding event occurred in 15 of 36 patients (42%) in the warfarin group and in 5 of 32 patients (16%) in the NOAC group (P = 0.032). Hospitalizations as a result of either a bleeding event or a thrombosis occurred in 19 of 36 patients (53%) in the warfarin group and in 8 of 32 patients (25%) in the NOAC group (P = 0.026). The majority of patients in the NOAC group (69%) received a reduced dose for the indication.

Conclusions: Warfarin increased the risk of major bleeding in patients with ESKD compared with NOACs and did not reduce the risk of thrombotic events.
Posted in: Nephrology and Urology25

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. January CT, Wann LS, Calkins 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. Circulation 2019;140:e125–e151.
 
2. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the Management of Atrial Fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893–2962.
 
3. Lip GYH, Banerjee A, Boriani G, et al. Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report. Chest 2018;154: 1121–1201.
 
4. 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;39:1330–1393.
 
5. Dahal K, Kunwar S, Rijal J, et al. Stroke, major bleeding, and mortality outcomes in warfarin users with atrial fibrillation and chronic kidney disease: a meta-analysis of observational studies. Chest 2016;149:951–959.
 
6. Harel Z, Chertow GM, Shah PS, et al. Warfarin and the risk of stroke and bleeding in patients with atrial fibrillation receiving dialysis: a systematic review and meta-analysis. Can J Cardiol 2017;33:737–746.
 
7. Nochaiwong S, Ruengorn C, Awiphan R, et al. Efficacy and safety of warfarin in dialysis patients with atrial fibrillation: a systematic review and meta-analysis. Open Heart 2016;3:e000441.
 
8. 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:e202175.
 
9. Tan J, Liu S, Segal JB, et al. Warfarin use and stroke, bleeding and mortality risk in patients with end stage renal disease and atrial fibrillation: a systematic review and meta-analysis. BMC Nephrol 2016;17:157.
 
10. Van Der Meersch H, De Bacquer D, De Vriese AS. Vitamin K antagonists for stroke prevention in hemodialysis patients with atrial fibrillation: a systematic review and meta-analysis. Am Heart J 2017;184:37–46.
 
11. Al-ani M, Parperis K. Warfarin-induced calciphylaxis. BMJ Case Rep 2016; 2016. DOI:10.1136/bcr-2015-214142.
 
12. Dias C, Moore KT, Murphy J, et al. Pharmacokinetics, pharmacodynamics, and safety of single-dose rivaroxaban in chronic hemodialysis. Am J Nephrol 2016;43:229–236.
 
13. Ionescu F, Cooper C, Petrescu I, et al. Safety of apixaban compared to warfarin in hemodialysis patients: do antiplatelets make a difference? Eur J Haematol 2021;106:689–696.
 
14. Reed D, Palkimas S, Hockman R, et al. Safety and effectiveness of apixaban compared to warfarin in dialysis patients. Res Pract Thromb Haemost 2018; 2:291–298.
 
15. Sarratt SC, Nesbit R, Moye R. Safety outcomes of apixaban compared with warfarin in patients with end-stage renal disease. Ann Pharmacother 2017; 51:445–450.
 
16. 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;138:1519–1529.
 
17. Wang X, Tirucherai G, Marbury TC, et al. Pharmacokinetics, pharmacodynamics, and safety of apixaban in subjects with end-stage renal disease on hemodialysis. J Clin Pharmacol 2016;56:628–636. .
 
18. Herzog CA, Asinger RW, Berger AK, et al. Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2011;80:572–586.
 
19. Eliquis (apixaban) [package insert]. Princeton, NJ: Bristol-Myers Squibb; 2019.
 
20. Xarelto (rivaroxaban) [package insert]. Titusville, NJ: Janssen Pharmaceuticals; 2021.
 
21. Pradaxa (dabigatran) [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals; 2020.
 
22. Savaysa (edoxaban) [package insert]. Basking Ridge, NJ: Daiichi Sankyo; 2020.
 
23. Christiansen CF, Schmidt M, Lamberg AL, et al. Kidney disease and risk of venous thromboembolism: a nationwide population-based case-control study. J Thromb Haemost 2014;12:1449–1454.
 
24. Molnar AO, Bota SE, McArthur E, et al. Risk and complications of venous thromboembolism in dialysis patients. Nephrol Dial Transplant 2018;33: 874–880.
 
25. Wattanakit K, CushmanM. Chronic kidney disease and venous thromboembolism: epidemiology and mechanisms. Curr Opin Pulm Med 2009;15:408–412.
 
26. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016;149:315–352.