Anticoagulant Use in Patients with Chronic Renal Impairment

Abstract

Patients with renal failure have an increased risk of both thrombotic and bleeding complications. A number of antithrombotic drugs undergo renal clearance. Therefore, estimation of renal function is necessary when prescribing these drugs to patients with renal dysfunction. Pharmacokinetic and clinical data in patients with chronic renal impairment are limited for several anticoagulants, and adequate administration information is often absent. Dose adjustment of anticoagulants may be indicated when the creatinine clearance falls below 30 mL/min. Unfractionated heparin, argatroban, and vitamin K antagonists generally do not require dose adjustment with renal dysfunction. However, smaller doses of warfarin may be required to achieve a particular target international normalized ratio. Close monitoring of anticoagulation is recommended when argatroban or high doses of unfractionated heparin are administered in patients with severe chronic renal impairment. Low-molecular weight heparins, danaparoid sodium, hirudins, and bivalirudin all undergo renal clearance. Lower doses and closer anticoagulation monitoring may be advisable when these agents are used in patients with chronic renal failure. We recommend that fondaparinux sodium and ximelagatran (not yet licensed) be avoided in the presence of severe renal impairment and be used with caution in patients with moderate renal dysfunction. While acknowledging the lack of pharmacokinetic data, this review provides specific recommendations for the use of anticoagulants in patients with chronic renal impairment.

2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation

“…Dlatego należy zmniejszyć dawkę podtrzymującą eptifibatidu z 2,0 do 1,0 µg/kg mc./min u pacjentów z eGFR < 50 ml/min/1,73 m [450].…”

Antithrombotic Therapy in Patients With Chronic Kidney Disease

“…73 Conversely, enoxaparin, the most extensively studied low-molecular-weight heparin, is eliminated predominantly via the renal pathway. Although monitoring of anticoagulation activity and dose adjustment of enoxaparin are not required in patients with stage 2 to 3 CKD, those with stage 4 CKD experience decreased clearance of enoxaparin and drug accumulation, leading to increased half-life, drug exposure, and bleeding risk.…”

“…76 Conversely, the clearance of fondaparinux decreases with increased renal impairment. 73,77 No dose reduction is required for patients with stage 2 to 3 CKD, whereas fondaparinux should be avoided in patients with stage 4 CKD. 78 Otamixaban, another parenteral factor X inhibitor under advanced phase clinical testing, exhibits mixed renal and biliary excretion with constant renal clearance.…”

The impact of bleeding in patients with acute coronary syndromes: How to optimize the benefits of treatment and minimize the risk

“…However, a recent evaluation (51) of low-molecular-weight heparin in patients with renal insufficiency determined that it was not possible to conclude that empirically dose-adjusted enoxaparin was not associated with increased risks for major bleeding events. Fondaparinux should also be avoided in patients with severe renal impairment (52). For patients with an eCrCl of less than 30 mL/min and an increased bleeding risk assessment, unfractionated heparin should be chosen until the safety of reduced-dose enoxaparin or fondaparinux in this population is shown.…”