What is the most appropriate anticoagulant for a patient with End-Stage Renal Disease (ESRD) on dialysis who develops a new Venous Thromboembolism (VTE)?

From the Guidelines

For patients with End-Stage Renal Disease (ESRD) on dialysis who develop a new Venous Thromboembolism (VTE), the most appropriate anticoagulant is generally not a low molecular weight heparin (LMWH) like enoxaparin due to its renal clearance and risk of bioaccumulation, but rather warfarin or, in certain cases, a heparin infusion, with warfarin being preferred due to its ease of monitoring and reversal, and lack of renal clearance. The recommended regimen typically involves initial bridging with unfractionated heparin (UFH) while simultaneously starting warfarin 1. UFH should be administered intravenously with a target aPTT of 1.5-2.5 times the control value, while warfarin is titrated to achieve an INR goal of 2-3. Once the INR is therapeutic for at least 24 hours, the heparin can be discontinued. Warfarin therapy should typically continue for at least 3-6 months, depending on whether the VTE was provoked or unprovoked. Some key points to consider in the management of VTE in patients with ESRD include:

• The risk of bleeding with anticoagulation in ESRD patients, which may be higher due to uremic platelet dysfunction and other factors 1
• The need for careful monitoring of anticoagulation therapy, including regular INR checks for warfarin and aPTT checks for UFH
• The potential for drug interactions with other medications that may be commonly used in ESRD patients, such as antibiotics and antiplatelet agents
• The importance of considering the patient's overall clinical condition, including their risk of recurrent VTE and bleeding, when making decisions about anticoagulation therapy. Direct oral anticoagulants (DOACs) such as apixaban, rivaroxaban, edoxaban, and dabigatran are either contraindicated or have limited data in dialysis patients, though apixaban may be considered in select cases at a reduced dose of 2.5mg twice daily based on emerging evidence. In terms of specific dosing recommendations, the manufacturer recommends monitoring of peak anti-Xa levels to achieve a target range of 0.5 to 1.5 IU/mL for patients with cancer with CCr less than 30 mL/min receiving dalteparin for extended treatment of acute VTE 1. However, the most appropriate choice for a patient with ESRD on dialysis who develops a new VTE is generally warfarin, with initial bridging with UFH, due to its ease of monitoring and reversal, and lack of renal clearance.

From the FDA Drug Label

Patients with End-Stage Renal Disease on Dialysis Clinical efficacy and safety studies with apixaban did not enroll patients with end-stage renal disease (ESRD) on dialysis. In patients with ESRD maintained on intermittent hemodialysis, administration of apixaban at the usually recommended dose [see Dosage and Administration (2. 1)] will result in concentrations of apixaban and pharmacodynamic activity similar to those observed in the ARISTOTLE study [see Clinical Pharmacology (12. 3)]. It is not known whether these concentrations will lead to similar stroke reduction and bleeding risk in patients with ESRD on dialysis as was seen in ARISTOTLE

The most appropriate anticoagulant for a patient with End-Stage Renal Disease (ESRD) on dialysis who develops a new Venous Thromboembolism (VTE) is not explicitly stated in the provided drug label. However, based on the information provided, apixaban may be considered, but with caution, as the clinical efficacy and safety studies did not enroll patients with ESRD on dialysis.

• Heparin infusion may be a more traditional choice for hospitalized patients with VTE, especially in patients with ESRD on dialysis.
• Enoxaparin and warfarin may also be considered, but their use in patients with ESRD on dialysis requires careful consideration of the potential risks and benefits.
• Apixaban 2 may be an option, but its use in this patient population is not well established.

From the Research

Anticoagulant Options for Patients with ESRD on Dialysis

The following anticoagulants are considered for a patient with End-Stage Renal Disease (ESRD) on dialysis who develops a new Venous Thromboembolism (VTE):

• Enoxaparin: However, a study 3 found that the difference in major or clinically relevant non-major bleeding rates between enoxaparin and unfractionated heparin (UFH) was not statistically significant, but the 6.8% bleed rate is concerning for inpatient enoxaparin usage.
• Heparin infusion: A study 4 reported that subcutaneous unfractionated heparin (UFH) is a safe and efficacious alternative for the treatment of VTE in patients with ESRD.
• Warfarin: Studies 5, 6, and 7 compared the safety and effectiveness of apixaban versus warfarin in patients with ESRD on dialysis and found that apixaban was associated with a lower risk of major bleeding, intracranial bleeding, and gastrointestinal bleeding.
• Apixaban: The same studies 5, 6, and 7 found that apixaban had a favorable risk-benefit profile, with significant reductions in ischemic stroke, major bleeding, and intracranial bleeding compared to warfarin in ESRD patients on hemodialysis with non-valvular AF and/or venous thromboembolism.

Comparison of Anticoagulants

Based on the studies, apixaban appears to be a safer and more effective option for patients with ESRD on dialysis who develop a new VTE, due to its lower risk of bleeding and thromboembolic events compared to warfarin. However, the choice of anticoagulant should be individualized based on patient-specific factors and clinical judgment.

Key Findings

• Apixaban is associated with a lower risk of major bleeding, intracranial bleeding, and gastrointestinal bleeding compared to warfarin in patients with ESRD on dialysis 5, 6, and 7.
• Enoxaparin may not be the best option due to concerns about drug accumulation and increased bleeding risk in patients with ESRD on dialysis 3.
• Subcutaneous unfractionated heparin (UFH) is a safe and efficacious alternative for the treatment of VTE in patients with ESRD 4.