What is the recommended approach for extended apixaban (apixaban) anticoagulation in cancer patients at high risk of thrombosis?

Extended Apixaban Anticoagulation in Cancer Patients at High Risk of Thrombosis

For cancer patients at high risk of thrombosis, extended anticoagulation with reduced-dose apixaban (2.5 mg twice daily) beyond 6 months is recommended as it is noninferior to full-dose apixaban (5 mg twice daily) for preventing recurrent venous thromboembolism while offering a lower risk of clinically relevant bleeding. 1

Risk Assessment and Initial Decision-Making

• Extended anticoagulation beyond the initial 6 months should be considered for patients with:

  • Active cancer still receiving treatment
  • High risk of recurrent thrombosis that outweighs bleeding risk 2
  • Residual DVT or index PE 2
  • Elevated D-dimer or C-reactive protein levels after anticoagulation interruption 2

• Regular risk-benefit assessment is crucial to ensure a favorable balance between thrombotic and bleeding risks 2

Anticoagulant Options for Extended Therapy

Apixaban

• Recommended regimen: 2.5 mg twice daily after completing 6 months of full-dose anticoagulation 1
• Evidence: The API-CAT trial demonstrated that reduced-dose apixaban was noninferior to full-dose (5 mg twice daily) for preventing recurrent VTE (2.1% vs 2.8%) while significantly reducing clinically relevant bleeding (12.1% vs 15.6%) 1
• Real-world data: Extended treatment with apixaban showed lower rates of recurrent VTE, major bleeding, and clinically relevant non-major bleeding compared to LMWH in cancer patients 3

Alternative Options

• LMWH: Traditionally preferred but requires daily injections
• Full-dose apixaban (5 mg twice daily): May be considered in patients at extremely high thrombotic risk with low bleeding risk
• Edoxaban or rivaroxaban: Alternative DOACs that can be considered 2

Important Considerations and Contraindications

Contraindications for Apixaban

• Severe renal impairment (CrCl <15 mL/min) 2, 4
• Hepatic impairment (transaminases >2× ULN or total bilirubin >1.5× ULN) 2
• Triple-positive antiphospholipid syndrome 2
• Pregnancy and lactation 2, 4

Special Populations

• Gastrointestinal cancers: Consider LMWH as first option due to potentially higher risk of GI bleeding with DOACs 2
• Urothelial cancers: LMWH may be preferred 2
• Drug interactions: Use caution with strong inhibitors/inducers of CYP3A4 and P-glycoprotein 2, 4
• Brain metastases: LMWH is preferred 2

Monitoring Protocol

• Regular assessment of:

  • Bleeding signs (unexplained bruising, blood in urine/stool, unusual headaches) 4
  • Renal and hepatic function 4
  • Thrombocytopenia
  • Drug interactions with cancer therapies
  • Cancer status and ongoing treatments

• Consider discontinuation if:

  • Cancer remission is achieved and maintained
  • Significant bleeding complications occur
  • Severe thrombocytopenia develops

Management of Complications

• Recurrent VTE despite anticoagulation:

  • Assess compliance
  • Rule out heparin-induced thrombocytopenia
  • Consider increasing to full-dose apixaban (5 mg twice daily)
  • Consider switching to LMWH 2
  • Consider adding vena cava filter in select cases 2

• Bleeding complications:

  • For minor bleeding: Consider temporary interruption
  • For major bleeding: Discontinue anticoagulation and consider reversal agents 2

Clinical Pearls

• The risk of recurrent VTE remains significant beyond 6 months in cancer patients, justifying extended anticoagulation 2
• Patient preference for oral medication versus injections should be considered when choosing between apixaban and LMWH 2
• Regular reassessment of cancer status, thrombotic risk, and bleeding risk is essential
• Incidental VTE should be treated the same as symptomatic VTE 2
• Vena cava filters should be reserved for patients with absolute contraindications to anticoagulation or recurrent VTE despite optimal anticoagulation 2