What alternative anticoagulation strategy is recommended for a patient with ESRD, history of DVT, CVA, and severe peripheral arterial disease, currently on clopidogrel (Plavix) and rivaroxaban (Xarelto)?

Discontinue Rivaroxaban and Transition to Warfarin

For this patient with ESRD on hemodialysis (CrCl <15 mL/min) and history of DVT, rivaroxaban must be discontinued immediately and replaced with warfarin (INR target 2.0-3.0), as rivaroxaban is contraindicated in end-stage renal disease and associated with significantly increased bleeding risk in dialysis patients. 1

Rationale for Discontinuation

• Rivaroxaban is explicitly contraindicated in ESRD with CrCl <15 mL/min per manufacturer labeling and multiple major guidelines 1
• Real-world data demonstrates that dabigatran and rivaroxaban in hemodialysis patients are associated with 48% and 38% higher rates of hospitalization or death from bleeding compared to warfarin, respectively 2
• The risk of hemorrhagic death specifically is 78% higher with dabigatran and 71% higher with rivaroxaban compared to warfarin in dialysis patients 2
• Rivaroxaban undergoes 33% renal elimination and bioaccumulates in ESRD, leading to unpredictable anticoagulant effects 3, 4

Recommended Anticoagulation Strategy

Primary Recommendation: Warfarin

• Initiate warfarin with target INR 2.0-3.0 for secondary prevention of DVT 1
• Warfarin is the anticoagulant of choice in ESRD as it does not rely on renal clearance 1
• Aim for time in therapeutic range (TTR) >65-70% with frequent INR monitoring 1
• Continue clopidogrel 75 mg daily for peripheral arterial disease, but recognize this substantially elevates bleeding risk when combined with warfarin 1

Alternative Option: Apixaban (If Warfarin Fails or Is Contraindicated)

• Apixaban 5 mg twice daily is the only DOAC approved by FDA for use in hemodialysis patients (specifically for atrial fibrillation indication) 1
• For VTE treatment in severe CKD, apixaban dosing would be 2.5 mg twice daily for extended therapy after initial treatment phase 5
• Multiple studies suggest apixaban may have lower bleeding and thromboembolic event rates compared to warfarin in ESRD patients 6
• Apixaban has the lowest renal elimination (27%) among DOACs, making it theoretically safer in renal impairment 1

Transition Protocol

Immediate Steps:

• Stop rivaroxaban immediately - do not wait for drug washout given ESRD 1
• Initiate warfarin at standard dosing (typically 5 mg daily, adjusted based on INR response) 1
• Overlap is not required when transitioning from rivaroxaban to warfarin in ESRD due to drug accumulation 3, 4
• Check baseline INR, CBC, and comprehensive metabolic panel 1

Monitoring:

• Check INR every 2-3 days initially until therapeutic range achieved 1
• Once stable, monitor INR at least monthly (more frequently in dialysis patients due to nutritional variability) 1
• Reassess renal function regularly even though patient is on dialysis, as residual function may decline 5
• Monitor for bleeding complications at every dialysis session 2

Critical Considerations for This Patient

Clopidogrel Continuation

• Continue clopidogrel 75 mg daily for severe peripheral arterial disease and CVA history 1
• The combination of warfarin plus clopidogrel carries significantly increased bleeding risk and requires close monitoring 1
• Consider holding clopidogrel temporarily during warfarin initiation if bleeding risk is deemed excessive, then reintroduce once INR is stable 1

VTE Indication Takes Priority

• This patient's history of DVT is the primary indication for anticoagulation, not the remote CVA 1, 5
• For unprovoked DVT, extended-duration anticoagulation is recommended with annual reassessment 1, 5
• The CVA history (if >1 year ago without atrial fibrillation) does not independently require anticoagulation 1

Common Pitfalls to Avoid

• Do not use rivaroxaban 15 mg or any reduced dose - even reduced dosing is contraindicated in ESRD 1
• Do not use dabigatran or edoxaban - these have even higher renal elimination than rivaroxaban 1
• Avoid NSAIDs completely - they increase bleeding risk and worsen residual renal function 5
• Do not assume apixaban is automatically safer than warfarin - while FDA-approved for hemodialysis in AF, evidence for VTE indication in ESRD is limited 6
• Monitor for drug interactions - many medications affect warfarin metabolism, particularly antibiotics commonly used in dialysis patients 4

Bleeding Risk Mitigation

• Assess bleeding risk at least annually using validated tools 5
• Ensure optimal blood pressure control (<130/80 mmHg) to reduce hemorrhagic stroke risk 1
• Coordinate with dialysis team regarding heparin use during dialysis sessions when patient is anticoagulated 2
• Consider proton pump inhibitor for GI bleeding prophylaxis given dual antithrombotic therapy 1