From the Guidelines
Extended apixaban therapy at full dose (5mg twice daily) is recommended for the secondary prevention of recurrent venous thromboembolism (VTE) due to its efficacy in reducing the incidence of fatal and non-fatal recurrent VTE, as supported by the American Society of Hematology 2020 guidelines 1. When considering extended apixaban therapy, it is essential to weigh the benefits of reduced recurrent VTE risk against the potential increased risk of bleeding. The decision to extend apixaban therapy at full dose should be individualized, taking into account the patient's risk factors for recurrence, such as unprovoked VTE, recurrent VTE, or ongoing risk factors like active cancer or certain thrombophilias.
- Key considerations for extended apixaban therapy include:
- Assessing the patient's bleeding risk, as prolonged anticoagulation increases this risk
- Regular monitoring and reassessment of the risk-benefit ratio, typically every 3-6 months
- Counseling patients on medication adherence, potential drug interactions, and signs of bleeding that warrant medical attention
- Periodic monitoring of kidney function, as dose adjustments may be necessary for patients with severe renal impairment Although the American Society of Hematology 2020 guidelines suggest that a lower dose of apixaban (2.5mg twice daily) may be used for secondary prevention, the evidence for this is based on studies that were not powered for comparisons between standard and low doses, and patients with higher risk of recurrence were excluded 1. Therefore, extended apixaban therapy at full dose is the preferred approach for secondary prevention of recurrent VTE, particularly for patients with higher risk of recurrence or those who have completed their initial treatment course.
From the FDA Drug Label
The AMPLIFY-EXT study enrolled patients with either an unprovoked DVT or PE at baseline (approximately 92%) or patients with a provoked baseline event and one additional risk factor for recurrence (approximately 8%) 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: 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 full dose of apixaban (5 mg bid) was associated with a reduced incidence of fatal or non-fatal recurrent venous thromboembolism compared to placebo, with a relative risk of 0.36 (95% CI 0.25,0.53) 2.
- The primary endpoint of symptomatic, recurrent VTE (nonfatal DVT or nonfatal PE), or all-cause death was lower in the apixaban 5 mg bid group (34 events, 4.2%) compared to the placebo group (96 events, 11.6%).
- The incidence of recurrent VTE was also lower in the apixaban 5 mg bid group (28 events, 3.4%) compared to the placebo group (72 events, 8.7%).
From the Research
Extended Apixaban Full Dose and Incidence of Fatal or Non-Fatal Recurrent Venous Thromboembolism
- The study 3 compared the effectiveness of extended treatment with a reduced dose of apixaban (2.5 mg) versus a full dose (5.0 mg) in preventing recurrent thromboembolic events in patients with active cancer and venous thromboembolism.
- The results showed that recurrent venous thromboembolism occurred in 18 patients (cumulative incidence, 2.1%) in the reduced-dose group and in 24 (cumulative incidence, 2.8%) in the full-dose group, with an adjusted subhazard ratio of 0.76 (95% confidence interval [CI], 0.41 to 1.41; P = 0.001 for noninferiority).
- Clinically relevant bleeding occurred in 102 patients (cumulative incidence, 12.1%) in the reduced-dose group and in 136 (cumulative incidence, 15.6%) in the full-dose group, with an adjusted subhazard ratio of 0.75 (95% CI, 0.58 to 0.97; P = 0.03).
- Another study 4 found that extended anticoagulation treatment with apixaban was associated with lower rates of recurrent venous thromboembolism, major bleeding, and clinically relevant nonmajor bleeding compared with low-molecular-weight heparin in adults with cancer-associated venous thromboembolism.
- The study 5 also found that apixaban patients had a lower risk of recurrent venous thromboembolism (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.47-0.81) and major bleeding (HR: 0.63; 95% CI: 0.47-0.86) versus low-molecular-weight heparin patients.
- However, the study 6 noted that the decision to extend anticoagulant treatment should be based on the risk of venous thromboembolism recurrence, the bleeding risk, and patient and physician preferences.
Risk of Recurrent Venous Thromboembolism
- The study 7 found that patients who experience a venous thromboembolism event in the absence of risk factors or who have persistent risk factors have a higher venous thromboembolism recurrence risk.
- The study 6 also noted that the risk of recurrence depends mostly on the presence of a risk factor for developing venous thromboembolism, with patients with unprovoked events being at the higher risk of recurrence.
- The study 3 found that extended anticoagulation with reduced-dose apixaban was noninferior to full-dose apixaban for the prevention of recurrent venous thromboembolism in patients with active cancer.
Bleeding Risk
- The study 3 found that the reduced dose of apixaban led to a lower incidence of clinically relevant bleeding complications than the full dose.
- The study 4 found that apixaban had lower adjusted incidence rates for major bleeding and clinically relevant nonmajor bleeding compared with low-molecular-weight heparin.
- The study 5 also found that apixaban patients had a lower risk of major bleeding compared with low-molecular-weight heparin patients.