Apixaban (Eliquis) Use in Cirrhosis
Apixaban can be safely used in patients with Child-Pugh A cirrhosis, should be used with caution in Child-Pugh B cirrhosis, and is not recommended in Child-Pugh C cirrhosis due to increased bleeding risk and limited clinical evidence. 1
Safety and Efficacy by Cirrhosis Severity
Child-Pugh A Cirrhosis
- Apixaban is considered safe and effective in Child-Pugh A cirrhosis 2, 1
- No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh class A) 3
- All major guidelines support the use of DOACs, including apixaban, in this population
Child-Pugh B Cirrhosis
- Use with caution in Child-Pugh B cirrhosis 2, 1
- Consider dose modification (reduction) in these patients 2
- The FDA label notes limited clinical experience with apixaban in these patients and acknowledges that patients with moderate hepatic impairment may have intrinsic coagulation abnormalities 3
- Among DOACs, apixaban appears to be preferred in this population, constituting 68% of DOAC use in cirrhotic patients as of 2019 2
Child-Pugh C Cirrhosis
- Apixaban is not recommended in Child-Pugh C cirrhosis 2, 1, 3
- The FDA explicitly states that apixaban is not recommended in patients with severe hepatic impairment (Child-Pugh class C) 3
Indications for Apixaban in Cirrhosis
Atrial Fibrillation: Apixaban is appropriate for stroke prevention in cirrhotic patients with atrial fibrillation (with appropriate CHA₂DS₂-VASc score) 1
Venous Thromboembolism (VTE): For treatment of DVT/PE in patients with cirrhosis 2
Portal Vein Thrombosis (PVT): May be considered for treatment or prophylaxis 1
Dosing Considerations
- Standard dosing for Child-Pugh A cirrhosis
- Consider dose reduction for Child-Pugh B cirrhosis 2
- Renal function: Consider dose reduction to 2.5mg twice daily if patient meets at least two criteria: Age ≥80 years, Body weight ≤60kg, or Serum creatinine ≥1.5mg/dL 1, 3
- Use with caution if creatinine clearance <30 mL/min 1
Advantages of Apixaban in Cirrhosis
- No routine laboratory monitoring required 1
- May have better safety profile compared to traditional anticoagulants like warfarin 2, 1
- Among DOACs, apixaban appears to have a better safety profile than rivaroxaban in patients with liver disease 2
- Higher persistence to treatment compared to vitamin K antagonists (31% vs 9% at 5 years) 2
Monitoring Recommendations
- Regular clinical assessment for bleeding signs is necessary 1
- Consider imaging every 3 months if treating portal vein thrombosis 1
- Avoid concomitant use with strong inhibitors of both CYP3A4 and P-glycoprotein 1
Alternative Anticoagulants
- For Child-Pugh B/C patients requiring anticoagulation, LMWH is often preferred 1
- LMWH is also preferred in patients with both renal failure and cirrhosis 1
Potential Risks and Complications
- Bleeding risk is a major concern, particularly non-variceal upper and lower intestinal bleeding 4
- Patients with hepatocellular carcinoma may have higher risk of major bleeding while on DOACs 4
- In patients with decompensated cirrhosis, significant bleeding and high rates of DOAC discontinuation have been reported with long-term use 4
Clinical Evidence Summary
Recent meta-analyses suggest that DOACs, including apixaban, may be associated with:
- Reduced risk of all-cause death (RR 0.78)
- Reduced risk of major bleeding (RR 0.68)
- Reduced risk of intracranial hemorrhage (RR 0.49) compared to warfarin in patients with liver disease 1
In the cirrhosis subgroup specifically, DOACs showed significantly reduced risks of:
- Major bleeding (RR 0.53)
- Gastrointestinal bleeding (RR 0.57)
- Intracranial hemorrhage (RR 0.55) compared to warfarin 1