Should Eliquis (apixaban) be discontinued after a provoked pulmonary embolism (PE)?

Should Eliquis Be Discontinued After a Provoked PE?

Yes, Eliquis (apixaban) should be discontinued after 3 months of treatment for a provoked pulmonary embolism, provided the provoking factor was major, transient, and has been eliminated. 1

Treatment Duration Based on Provoking Factor Type

Major Transient/Reversible Risk Factors (Surgery, Major Trauma)

• Discontinue anticoagulation after 3 months of therapeutic treatment 1
• These patients have a very low annual recurrence risk (<1%) after completing 3 months of anticoagulation 1
• The 2019 European Society of Cardiology guidelines give this a Class I, Level B recommendation 1

Minor Transient or Non-Surgical Risk Factors

• The recurrence risk falls between that of unprovoked VTE and surgery-provoked VTE 1
• Consider extended anticoagulation of indefinite duration for these patients 1
• The decision should be influenced by individual bleeding risk assessment 1

Hormone-Associated PE

• Discontinue anticoagulation after 3-6 months if hormonal therapy is stopped at the time of diagnosis 1
• These patients have approximately 50% lower recurrence risk compared to unprovoked VTE 1
• Hormonal therapy should be discontinued before stopping anticoagulation 1

Critical Decision Algorithm

Step 1: Identify the provoking factor

• Major surgery or major trauma = proceed to discontinuation after 3 months 1
• Minor transient factor or non-surgical = assess for enduring risk factors 1, 2
• No identifiable factor = treat as unprovoked (extended therapy recommended) 1

Step 2: Assess for enduring risk factors

• Obesity, heart failure, chronic inflammatory conditions, or other persistent factors may increase recurrence risk even with initial provoking factor 3, 2
• Recent evidence from the HI-PRO trial (2025) showed that patients with provoked VTE plus enduring risk factors had 10% recurrence rate with placebo versus 1.3% with low-dose apixaban (2.5 mg twice daily) over 12 months 2

Step 3: Bleeding risk assessment

• High bleeding risk patients should stop after 3 months even with higher recurrence risk 1
• Low to moderate bleeding risk patients with enduring factors should consider extended therapy 1, 2

Important Caveats and Common Pitfalls

Do Not Confuse Provoked with Unprovoked

• The distinction between provoked and unprovoked PE is the strongest predictor of recurrence risk 1
• A truly provoked PE from major surgery has <1% annual recurrence risk, while unprovoked PE has >5% annual recurrence risk 1

Premature Discontinuation Warning

• The FDA label for apixaban includes a boxed warning that premature discontinuation increases thrombotic event risk 4
• If stopping anticoagulation for reasons other than completion of therapy, consider coverage with another anticoagulant 4

Presence of Enduring Risk Factors Changes Management

• Even with a clear provoking factor, the presence of enduring risk factors (obesity, heart failure, chronic inflammatory disease) may warrant extended therapy 3, 2
• The 2025 HI-PRO trial demonstrated significant benefit of low-dose apixaban (2.5 mg twice daily) for 12 months in this population, with hazard ratio of 0.13 for recurrent VTE 2

Reassessment is Essential

• Patients on extended anticoagulation require periodic reassessment of bleeding risk, drug tolerance, renal and hepatic function 1
• The 2019 ESC guidelines recommend this as a Class I recommendation 1

Specific Guidance for Extended Therapy When Indicated

If extended therapy is chosen (for minor provoking factors with enduring risks):

• Use reduced-dose apixaban 2.5 mg twice daily after completing 6 months of therapeutic anticoagulation 1
• This reduced dose provides effective VTE prevention with lower bleeding risk compared to full therapeutic dosing 1
• The 2021 CHEST guidelines give this a weak recommendation with very low-certainty evidence 1