Chronic Kidney Disease and Anticoagulation: from Vitamin K Antagonists and Heparins to Direct Oral Anticoagulant Agents

Overview

Journal Intern Emerg Med

Publisher Springer

Specialties Emergency Medicine
General Medicine

Date 2017 Sep 21

PMID 28929298

Citations 8

Authors

Savino Sciascia

Massimo Radin

Karen Schreiber

Roberta Fenoglio

Simone Baldovino

Dario Roccatello

Affiliations

Soon will be listed here.

Abstract

Anticoagulation in patients with impaired kidney function can be challenging since drugs' pharmacokinetics and bioavailability are altered in this setting. Patients with chronic kidney disease (CKD) treated with conventional anticoagulant agents [vitamin K antagonist (VKA), low-molecular weight heparin (LMWH) or unfractionated heparin (UFH)] are at high risk of bleeding events (both non-major and major clinically relevant bleeding). While anticoagulation reduces the risk of thromboembolic events, the co-existing bleeding risk and the fact that the most commonly used anticoagulation agents are eliminated via the kidneys pose additional challenges. More recently, two classes of direct oral anticoagulant agents (DOACs) have been investigated for the prevention and management of venous thromboembolic events: the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban, and the direct thrombin inhibitor dabigatran. In this review, we discuss the complex challenges and the practical considerations associated with the management of anticoagulation treatment in patients with CKD, with a special focus on DOACs.

Citing Articles

Anticoagulation in Chronic Kidney Disease.

Montomoli M, Candia B, Barrios A, Bernat E Drugs. 2024; 84(10):1199-1218.

PMID: 39120783 DOI: 10.1007/s40265-024-02077-6.

Therapeutic anticoagulation complications in the elderly: a case report.

Niemann M, Braun K, Ahmad S, Eder C, Stockle U, Graef F BMC Geriatr. 2022; 22(1):102.

PMID: 35123396 PMC: 8817490. DOI: 10.1186/s12877-022-02781-6.

Optimization of Heparin Monitoring with Anti-FXa Assays and the Impact of Dextran Sulfate for Measuring All Drug Activity.

Amiral J, Amiral C, Dunois C Biomedicines. 2021; 9(6).

PMID: 34205548 PMC: 8235539. DOI: 10.3390/biomedicines9060700.

The use of anticoagulants in chronic kidney disease: Common point of view of cardiologists and nephrologists.

Domienik-Karlowicz J, Tronina O, Lisik W, Durlik M, Pruszczyk P Cardiol J. 2019; 27(6):868-874.

PMID: 30912573 PMC: 8079097. DOI: 10.5603/CJ.a2019.0025.

Anticoagulation in CKD and ESRD.

Leung K, MacRae J J Nephrol. 2019; 32(5):719-731.

PMID: 30689127 DOI: 10.1007/s40620-019-00592-4.

References

Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E . The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004; 126(3 Suppl):204S-233S. DOI: 10.1378/chest.126.3_suppl.204S. View

Dans A, Connolly S, Wallentin L, Yang S, Nakamya J, Brueckmann M . Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Circulation. 2012; 127(5):634-40. DOI: 10.1161/CIRCULATIONAHA.112.115386. View

Trujillo-Santos J, Schellong S, Falga C, Zorrilla V, Gallego P, Barron M . Low-molecular-weight or unfractionated heparin in venous thromboembolism: the influence of renal function. Am J Med. 2013; 126(5):425-434.e1. DOI: 10.1016/j.amjmed.2012.09.021. View

Oldgren J, Budaj A, Granger C, Khder Y, Roberts J, Siegbahn A . Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial. Eur Heart J. 2011; 32(22):2781-9. DOI: 10.1093/eurheartj/ehr113. View

Raschi E, Bianchin M, Fantoni C, Ageno W, De Ponti F, De Ponti R . Evolving cardiovascular uses of direct-acting oral anticoagulants: a paradigm shift on the horizon?. Intern Emerg Med. 2017; 12(7):923-934. DOI: 10.1007/s11739-017-1724-7. View

Mendell J, Zahir H, Matsushima N, Noveck R, Lee F, Chen S . Drug-drug interaction studies of cardiovascular drugs involving P-glycoprotein, an efflux transporter, on the pharmacokinetics of edoxaban, an oral factor Xa inhibitor. Am J Cardiovasc Drugs. 2013; 13(5):331-42. PMC: 3781304. DOI: 10.1007/s40256-013-0029-0. View

Ahmad Y, Lip G . Dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation: NICE guidance. Heart. 2012; 98(19):1404-6. DOI: 10.1136/heartjnl-2012-302101. View

Antman E, Cohen M, Radley D, McCabe C, Rush J, Premmereur J . Assessment of the treatment effect of enoxaparin for unstable angina/non-Q-wave myocardial infarction. TIMI 11B-ESSENCE meta-analysis. Circulation. 1999; 100(15):1602-8. DOI: 10.1161/01.cir.100.15.1602. View

Giugliano R, Ruff C, Braunwald E, Murphy S, Wiviott S, Halperin J . Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013; 369(22):2093-104. DOI: 10.1056/NEJMoa1310907. View

10.

Scaglione F . New oral anticoagulants: comparative pharmacology with vitamin K antagonists. Clin Pharmacokinet. 2013; 52(2):69-82. DOI: 10.1007/s40262-012-0030-9. View

11.

Stangier J, Rathgen K, Stahle H, Mazur D . Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet. 2010; 49(4):259-68. DOI: 10.2165/11318170-000000000-00000. View

12.

Chan K, Lazarus J, Thadhani R, Hakim R . Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation. J Am Soc Nephrol. 2009; 20(10):2223-33. PMC: 2754104. DOI: 10.1681/ASN.2009030319. View

13.

Juma S, Thomson B, Lok C, Clase C, Blake P, Moist L . Warfarin use in hemodialysis patients with atrial fibrillation: decisions based on uncertainty. BMC Nephrol. 2013; 14:174. PMC: 3751624. DOI: 10.1186/1471-2369-14-174. View

14.

Diez-Manglano J, Bernabeu-Wittel M, Murcia-Zaragoza J, Escolano-Fernandez B, Jarava-Rol G, Hernandez-Quiles C . Oral anticoagulation in patients with atrial fibrillation and medical non-neoplastic disease in a terminal stage. Intern Emerg Med. 2016; 12(1):53-61. DOI: 10.1007/s11739-016-1517-4. View

15.

Kleinow M, Garwood C, Clemente J, Whittaker P . Effect of chronic kidney disease on warfarin management in a pharmacist-managed anticoagulation clinic. J Manag Care Pharm. 2011; 17(7):523-30. PMC: 10437548. DOI: 10.18553/jmcp.2011.17.7.523. View

16.

Sardar P, Chatterjee S, Lavie C, Giri J, Ghosh J, Mukherjee D . Risk of major bleeding in different indications for new oral anticoagulants: insights from a meta-analysis of approved dosages from 50 randomized trials. Int J Cardiol. 2014; 179:279-87. DOI: 10.1016/j.ijcard.2014.11.101. View

17.

Kakkos S, Kirkilesis G, Tsolakis I . Editor's Choice - efficacy and safety of the new oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban in the treatment and secondary prevention of venous thromboembolism: a systematic review and meta-analysis of phase III trials. Eur J Vasc Endovasc Surg. 2014; 48(5):565-75. DOI: 10.1016/j.ejvs.2014.05.001. View

18.

Mega J, Braunwald E, Murphy S, Plotnikov A, Burton P, Kiss R . Rivaroxaban in patients stabilized after a ST-segment elevation myocardial infarction: results from the ATLAS ACS-2-TIMI-51 trial (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary.... J Am Coll Cardiol. 2013; 61(18):1853-9. DOI: 10.1016/j.jacc.2013.01.066. View

19.

Buller H, Decousus H, Grosso M, Mercuri M, Middeldorp S, Prins M . Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013; 369(15):1406-15. DOI: 10.1056/NEJMoa1306638. View

20.

Crowther M, Lim W . Low molecular weight heparin and bleeding in patients with chronic renal failure. Curr Opin Pulm Med. 2007; 13(5):409-13. DOI: 10.1097/MCP.0b013e328216430d. View