When to continue Eliquis (apixaban) therapy in patients with a history of thromboembolic events?

Duration of Eliquis (Apixaban) Therapy After Thromboembolic Events

For patients with unprovoked VTE (DVT or PE) and low-to-moderate bleeding risk, extended anticoagulation with apixaban without a scheduled stop date is recommended over stopping at 3 months, with annual reassessment of the risk-benefit ratio. 1

Initial Treatment Phase (First 3 Months)

All patients with VTE should complete at least 3 months of anticoagulation therapy, which represents the "active treatment" phase addressing the acute thrombotic event. 1 After this initial period, the decision to continue or stop anticoagulation depends primarily on whether the VTE was provoked or unprovoked, and secondarily on bleeding risk. 1

Decision Algorithm Based on VTE Characteristics

Provoked VTE (Major Transient Risk Factor)

Stop anticoagulation after 3 months if the VTE was provoked by a major transient risk factor such as surgery or major trauma. 1 These patients have low recurrence risk (approximately 5.6 per 100 patient-years) and do not benefit from extended therapy. 1

Provoked VTE (Minor Transient Risk Factor)

Consider stopping anticoagulation after 3 months for VTE provoked by minor transient risk factors, though this is a weaker recommendation. 1 The recurrence risk is intermediate between major provoked and unprovoked VTE. 1

Unprovoked VTE or VTE with Persistent Risk Factors

Offer extended-phase anticoagulation without a scheduled stop date for patients with:

• First unprovoked proximal DVT or PE 1
• Unprovoked isolated distal DVT (if initially treated with anticoagulation) 1
• VTE associated with persistent risk factors 1

This recommendation is strongest for patients with low-to-moderate bleeding risk. 1

Bleeding Risk Stratification

Low Bleeding Risk

Recommend extended anticoagulation for unprovoked VTE. 1 The benefits of preventing recurrent VTE (which carries mortality risk of 5-10% for PE) outweigh bleeding risks. 1

Moderate Bleeding Risk

Suggest extended anticoagulation for unprovoked VTE, though this is a conditional recommendation requiring careful patient discussion. 1

High Bleeding Risk

Recommend stopping anticoagulation at 3 months even for unprovoked VTE, as bleeding risks outweigh benefits. 1 High bleeding risk includes active bleeding disorders, recent major bleeding, or conditions predisposing to severe bleeding. 1

Special Populations

Cancer-Associated Thrombosis

Recommend extended anticoagulation without a scheduled stop date regardless of bleeding risk (strong recommendation for low-moderate bleeding risk, conditional for high bleeding risk). 1 Cancer patients have persistently elevated recurrence risk. 1

Second Unprovoked VTE

Strongly recommend extended anticoagulation for patients with recurrent unprovoked VTE, even with moderate bleeding risk. 1 Only patients with high bleeding risk should consider stopping at 3 months. 1

History of Both Provoked and Unprovoked VTE

Continue anticoagulation if a patient with prior unprovoked VTE develops a new provoked VTE. 1 The unprovoked event history indicates ongoing thrombotic risk. 1

Optimal Dosing for Extended Therapy

For extended-phase anticoagulation beyond 6 months of treatment:

Reduced-dose apixaban (2.5 mg twice daily) is suggested over full-dose (5 mg twice daily) for secondary prevention. 1, 2 This provides effective VTE prevention with potentially lower bleeding risk. 1

The standard treatment dose (5 mg twice daily after initial 10 mg twice daily for 7 days) should be used for the first 6 months. 2

Factors Strengthening the Decision for Extended Therapy

The following factors favor continuing anticoagulation after unprovoked VTE:

• Male sex (higher recurrence risk than females) 1, 3
• PE rather than DVT as the index event (higher mortality risk with recurrence) 3
• Positive D-dimer measured 1 month after stopping anticoagulation (indicates ongoing thrombotic activity) 1, 3

Mandatory Reassessment

All patients on extended anticoagulation must have the decision reassessed at least annually, evaluating changes in bleeding risk, patient preference, and clinical status. 1 Extended therapy does not mean "never stop"—it means no predetermined stop date with ongoing evaluation. 1

When Hematology Referral is Appropriate

Consider hematology referral for:

• Recurrent VTE on therapeutic anticoagulation (breakthrough events require evaluation for underlying thrombophilia, malignancy, or antiphospholipid syndrome) 1
• Uncertain provocation status where classification as provoked vs unprovoked is unclear 1
• Young patients (<50 years) with unprovoked VTE who may require decades of anticoagulation 3
• Patients with suspected thrombophilia affecting treatment decisions 1

Critical Pitfalls to Avoid

Do not use arbitrary time limits (e.g., 6,12, or 24 months) for unprovoked VTE—the choice is 3 months or indefinite. 1 Intermediate durations are not supported by evidence. 1

Do not withhold extended anticoagulation solely based on bleeding risk scores without considering the life-threatening nature of recurrent PE. 1 The decision requires balancing individual bleeding and thrombotic risks. 1

Do not assume aspirin is an adequate alternative to anticoagulation for patients who want extended therapy—aspirin is much less effective and only considered if the patient refuses anticoagulation. 1

Do not forget that apixaban affects INR, so transitioning to warfarin requires using a parenteral anticoagulant bridge until therapeutic INR is achieved. 2