Do patients with unprovoked pulmonary embolism (PE) remain on apixaban (eliquis) for life?

Anticoagulation Duration for Unprovoked Pulmonary Embolism

Patients with unprovoked pulmonary embolism (PE) should receive indefinite (potentially lifelong) anticoagulation with apixaban due to their high risk of recurrence (>5% annually). 1, 2

Risk Stratification and Treatment Duration

The duration of anticoagulation therapy for PE depends primarily on whether the event was provoked or unprovoked:

• Provoked PE with major transient risk factors (e.g., surgery):

  • 3 months of anticoagulation is sufficient 1
  • Low recurrence risk (<1% annually) after treatment completion

• Provoked PE with minor transient risk factors:

  • 3-6 months of anticoagulation 1
  • Intermediate recurrence risk

• Unprovoked PE:

  • Initial treatment: 3-6 months 2, 1
  • Extended treatment: Indefinite anticoagulation 2, 1
  • High recurrence risk (>5% annually) after discontinuation

Rationale for Indefinite Anticoagulation in Unprovoked PE

The decision for indefinite anticoagulation in unprovoked PE is based on several key factors:

1. High recurrence risk: Patients with unprovoked PE have an annual risk of recurrence >5% after stopping anticoagulation 2, 1

2. Continued benefit only during treatment: The protective effect of anticoagulation continues only as long as therapy is maintained 2, 1

3. Recurrence pattern: In patients with previous PE, recurrence tends to manifest as PE rather than DVT, carrying higher mortality risk 2

4. Risk-benefit ratio: The risk of recurrent VTE generally exceeds the risk of anticoagulation-related bleeding in most patients with unprovoked PE 2

Apixaban for Extended Treatment

For extended anticoagulation with apixaban beyond the initial 6 months:

• Consider reduced dose of apixaban (2.5 mg twice daily) after at least 6 months of therapeutic anticoagulation to maintain efficacy while reducing bleeding risk 1

• Full-dose apixaban (5 mg twice daily) may be continued in patients with high recurrence risk and low bleeding risk 2

Monitoring and Reassessment

For patients on indefinite anticoagulation:

• Regular assessment of bleeding risk, drug tolerance, and adherence 1
• Periodic monitoring of hepatic and renal function 1
• Reassessment of the risk-benefit ratio for continuing therapy

Bleeding Risk Considerations

Factors that increase bleeding risk and may influence the decision for indefinite anticoagulation:

• Advanced age
• Previous bleeding
• Cancer
• Renal or hepatic impairment
• Concomitant antiplatelet therapy
• Poor anticoagulation control
• Comorbidities
• Recent surgery
• Frequent falls or alcohol abuse 1

Special Situations

• Second unprovoked VTE: Definite indication for indefinite anticoagulation 1, 3
• Cancer-associated PE: Anticoagulation for at least 6 months, and extended if cancer remains active 1, 4
• Hormone-associated PE: Can stop after 3 months if hormone therapy is discontinued, but should continue for the duration of hormone therapy 1

The European Society of Cardiology, International Society on Thrombosis and Haemostasis, and other major guidelines consistently recommend indefinite anticoagulation for unprovoked PE due to the high risk of recurrence after discontinuation and the favorable risk-benefit profile of extended anticoagulation, particularly with direct oral anticoagulants like apixaban 2, 1, 5.