Can apixaban (apixaban) be given for 12 more months in patients with provoked Venous Thromboembolism (VTE) and enduring risk factors, particularly those with heart failure?

Extended Anticoagulation with Apixaban for Provoked VTE with Enduring Risk Factors

For patients with provoked VTE and enduring risk factors, including heart failure, extended anticoagulation with reduced-dose apixaban (2.5 mg twice daily) for 12 months is recommended as it significantly reduces the risk of recurrent VTE with minimal bleeding risk. 1

Classification of VTE and Risk Factors

• VTE can be categorized based on provoking factors, which affects decisions about extended anticoagulation: 2

  • Major transient risk factors (e.g., surgery, trauma)
  • Minor transient risk factors
  • Persistent risk factors (including heart failure)
  • Unprovoked VTE

• Heart failure is considered a persistent risk factor that increases the risk of recurrent VTE even after the initial treatment period 1

Evidence for Extended Anticoagulation in Provoked VTE with Enduring Risk Factors

• The 2024 HI-PRO trial specifically addressed this question, showing that in patients with provoked VTE and enduring risk factors (including heart failure), apixaban 2.5 mg twice daily for 12 months resulted in: 1

  • 87% reduction in recurrent VTE compared to placebo (1.3% vs 10.0%)
  • Very low risk of major bleeding (only 1 patient in the apixaban group)
  • No deaths attributed to cardiovascular or hemorrhagic causes

• CHEST guidelines recommend: 2

  • Against extended anticoagulation for VTE with major transient risk factors alone
  • Extended anticoagulation for VTE with persistent risk factors

• For patients selected for extended anticoagulation, reduced-dose apixaban (2.5 mg twice daily) is preferred over full-dose regimens due to: 2

  • Similar efficacy in preventing recurrent VTE
  • Lower bleeding risk (10 fewer bleeding events per 1,000 cases)

Duration of Extended Anticoagulation

• Extended-phase anticoagulation does not have a predefined stop date, but most studies followed patients for 2-4 years 2

• Patients receiving extended anticoagulation should be reassessed: 2

  • At least annually
  • At times of significant health status changes
  • For bleeding risk, treatment burden, and any changes in patient preferences

Special Considerations for Heart Failure

• Heart failure is specifically recognized as a persistent risk factor that increases VTE recurrence risk 1

• The HI-PRO trial included heart failure patients among those with enduring risk factors who benefited from extended anticoagulation 1

• The risk-benefit ratio strongly favors extended anticoagulation with reduced-dose apixaban in patients with heart failure and a history of provoked VTE 1

Implementation Algorithm

1. For patients with provoked VTE who have completed at least 3 months of therapeutic anticoagulation: 1

   • Assess for presence of enduring risk factors (including heart failure)
   • Evaluate bleeding risk

2. If enduring risk factors are present with acceptable bleeding risk: 1

   • Transition to apixaban 2.5 mg twice daily for extended treatment
   • Plan for at least 12 months of therapy

3. Monitor periodically: 2

   • Reassess bleeding risk at least annually
   • Evaluate for signs/symptoms of recurrent VTE
   • Consider continuing beyond 12 months based on persistent risk factors

Common Pitfalls and Caveats

• Not recognizing heart failure as a persistent risk factor that warrants extended anticoagulation 1

• Using full-dose anticoagulation for extended therapy when reduced-dose is equally effective with less bleeding risk 2

• Failing to reassess the risk-benefit balance periodically during extended anticoagulation 2

• The risk-to-benefit balance of continuing anticoagulants beyond 4 years is less certain and requires individualized assessment 2

• Patients with multiple previous VTE episodes may have higher recurrence risk even on low-dose DOACs and may require closer monitoring 3