What is the incidence of recurrent Venous Thromboembolism (VTE) with extended Apixaban (apixaban) therapy?

From the Guidelines

Extended apixaban therapy at a dose of 2.5 mg twice daily is recommended for patients at high risk of recurrent venous thromboembolism (VTE) after completing their initial treatment course, as it reduces the risk of recurrent VTE by approximately 80% compared to placebo, with a relatively low bleeding risk. This recommendation is based on the most recent and highest quality study available, which demonstrated the efficacy and safety of extended apixaban therapy in preventing recurrent VTE 1. The study found that extended anticoagulant therapy, including apixaban, can reduce recurrent VTE by more than 80%, with a risk of bleeding similar to that of aspirin.

Key Points to Consider

• Patients who would benefit most from extended apixaban therapy include those with unprovoked VTE, recurrent VTE, active cancer, or persistent risk factors.
• The optimal duration of extended therapy varies by patient, but many experts suggest reassessing the need for continued anticoagulation annually.
• Regular monitoring and reassessment of the risk-benefit ratio is essential for patients on extended apixaban therapy, particularly in elderly patients or those with renal impairment.
• The mechanism behind apixaban's effectiveness involves its selective inhibition of factor Xa, which prevents thrombin formation and subsequent clot development.

Evidence-Based Recommendations

The American Society of Hematology (ASH) guideline panel has provided a conditional recommendation that the standard dose or the lower dose of rivaroxaban or apixaban may be used for the secondary prevention of VTE 1. However, the most recent study suggests that extended apixaban therapy at a dose of 2.5 mg twice daily is a viable option for patients at high risk of recurrence, with a relatively low bleeding risk 1. The study also notes that aspirin therapy may be less effective in reducing recurrent VTE, with a risk reduction of about one-third, compared to extended anticoagulant therapy.

Clinical Implications

In clinical practice, the decision to extend apixaban therapy should be individualized, taking into account the patient's risk of recurrence, bleeding risk, and other comorbidities. The benefits of extended apixaban therapy, including the reduction of recurrent VTE, should be weighed against the potential risks, including bleeding, and regular monitoring and reassessment of the risk-benefit ratio is essential. As noted in the study by Agnelli et al, the use of apixaban 2.5 mg twice-daily dose vs placebo resulted in a significant reduction in recurrent VTE, with a relative risk of 0.19 (0.11-0.33) 1.

From the FDA Drug Label

In the AMPLIFY-EXT study, both doses of apixaban were superior to placebo in the primary endpoint of symptomatic, recurrent VTE (nonfatal DVT or nonfatal PE), or all-cause death (Table 14). Table 14: Efficacy Results in the AMPLIFY-EXT Study Apixaban 2.5 mg bid N=840 Apixaban 5 mg bid N=813 Placebo N=829 Relative Risk (95% CI) Apixaban 2.5 mg bid vs Placebo Apixaban 5 mg bid vs Placebo n Recurrent VTE or all- cause death DVT* PE* All-cause death 32 (3.8) 19 (2.3) 23 (2.7) 22 (2.6) 34 (4.2) 28 (3.4) 25 (3.1) 25 (3.1) 96 (11.6) 72 (8.7) 37 (4.5) 33 (4.0) 0.33 (0.22,0.48) p<0.0001 0.36 (0.25,0.53) p<0. 0001

The incidence of recurrent VTE was lower in patients treated with apixaban compared to placebo in the AMPLIFY-EXT study.

• The relative risk of recurrent VTE or all-cause death was 0.33 (0.22,0.48) for apixaban 2.5 mg bid vs placebo, and 0.36 (0.25,0.53) for apixaban 5 mg bid vs placebo.
• The number of patients with recurrent VTE or all-cause death was 32 (3.8%) for apixaban 2.5 mg bid, 34 (4.2%) for apixaban 5 mg bid, and 96 (11.6%) for placebo. The results suggest that extended treatment with apixaban reduces the risk of recurrent VTE compared to placebo 2.

From the Research

Extended Apixaban and Incidence of Recurrent VTE

• The use of extended apixaban has been shown to reduce the risk of recurrent venous thromboembolism (VTE) without increasing the risk of major bleeding 3, 4, 5.
• A study comparing the effectiveness and safety of low-dose (2.5 mg twice daily) versus full-dose (5 mg twice daily) apixaban during extended phase oral anticoagulation found no detected differences in recurrent VTE or major bleeding events between the two groups 6.
• Another study found that extended apixaban use was associated with decreased risks of recurrent VTE and mortality, without increased major bleeding risk, compared to no extended treatment or warfarin 4.
• The use of low-dose apixaban (2.5 mg twice daily) has been shown to be effective and safe for secondary prophylaxis of VTE in major-thrombophilia carriers, with no increase in VTE recurrence and/or bleeding risk 7.
• Overall, the evidence suggests that extended apixaban is a safe and effective treatment option for reducing the risk of recurrent VTE, with a favorable benefit-risk profile compared to other anticoagulants 3, 6, 4, 5, 7.

Dosage and Efficacy

• The optimal dose of apixaban for extended phase therapy is still being studied, but low-dose (2.5 mg twice daily) and full-dose (5 mg twice daily) regimens have been shown to be effective in reducing the risk of recurrent VTE 6, 5.
• A study found that apixaban 2.5 mg twice daily is an alternative option for extended phase therapy for risk reduction of VTE recurrence compared to apixaban 5 mg twice daily 6.
• The use of low-dose apixaban has been shown to be effective and safe in secondary VTE prophylaxis for carriers of major thrombophilia, with no increase in VTE recurrence and/or bleeding risk 7.

Safety Profile

• The safety profile of apixaban has been extensively studied, and it has been shown to have a favorable benefit-risk profile compared to other anticoagulants 3, 4, 5.
• The risk of major bleeding with apixaban is low, and it has been shown to be similar to or lower than that of other anticoagulants 3, 6, 4, 5.
• The use of low-dose apixaban has been shown to be safe, with no increase in major bleeding risk, in secondary VTE prophylaxis for carriers of major thrombophilia 7.