Use of Newer Anticoagulants in Patients With Chronic Kidney Disease

Bob L. Lobo

Disclosures

Am J Health Syst Pharm. 2007;64(19):2017-2026. 

In This Article

Abstract and Introduction

Purpose: The current indications, dosing, and practical considerations for use of newer anticoagulants in patients with various degrees of renal impairment who do not require dialysis are reviewed.
Summary: Kidney function should generally be evaluated in all patients commencing anticoagulant therapy. As in the general population, hospitalized patients with impaired renal function most often have impairment that is mild to moderate in severity. Drug dosing in patients with chronic kidney disease may require that adjustment be made to the usual loading or maintenance dose of a drug. Newer anticoagulants with labeling approved by the Food and Drug Administration for venous thromboembolism (VTE) prophylaxis, treatment, or both include the low-molecular-weight heparins (LMWHs) and the factor Xa inhibitor fondaparinux. Some LMWHs are also indicated for the management of patients with acute coronary syndrome (ACS). All of the newer anticoagulants currently available for the management of VTE and ACS have approved labeling for use in patients with mild-to-moderate renal impairment. Currently available LMWHs, factor Xa inhibitors, and direct thrombin inhibitors (excluding argatroban) are eliminated primarily by the kidneys, so dosing in patients with severe renal impairment may require cautious dosage reduction or increased monitoring for bleeding and thromboembolic complications or both. Unfractionated heparin is the preferred anticoagulant for use in most of these patients.
Conclusion: Newer anticoagulants should be used with caution in patients with mild-to-moderate renal impairment. Unfractionated heparin remains the preferred anticoagulant in most patients with severe renal impairment even though its use is associated with increased bleeding in this population. Dosing of newer anticoagulants, except argatroban, requires cautious dosage reduction and increased monitoring for complications.

Several alternatives to traditional anticoagulants have become available in the United States for the prevention and treatment of venous thromboembolism (VTE) and for the management of acute coronary syndrome (ACS).[1] Most of these newer anticoagulants are eliminated primarily by the kidneys;[1,2] therefore, they have the potential to accumulate in patients with impaired renal function and increase the risk of bleeding, the major complication of anticoagulant therapy.[2,3]

The potential for increased bleeding in patients receiving anticoagulants is a serious safety concern. In one study of hospitalized patients with anticoagulant-related major hemorrhage, patients with excessive anticoagulation had a greater than twofold increase in 60-day mortality compared with patients with nonexcessive anticoagulation.[4] Safety concerns may lead clinicians to inappropriately withhold anticoagulants in patients with renal impairment who might benefit from treatment. A recent analysis from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) Quality Improvement Initiative, a large study involving 45,343 patients with non-ST-segment ACS, found that clinicians treating patients with chronic kidney disease (CKD) had lower adherence to the ACS treatment guidelines than did patients with normal renal function.[5] Even though the presence of moderate-to-severe CKD in patients with ACS increased the risk of mortality by 50%, these patients were significantly less likely to be treated with medications or undergo invasive cardiac procedures than patients with normal renal function.[5] Appropriate anticoagulation in patients with renal impairment requires that the patient's risk of thrombosis be carefully balanced against the risk of bleeding.

This article discusses the current indications, dosing, and practical implications for use of newer anticoagulants in patients with various degrees of renal impairment who do not require dialysis.

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