From the Guidelines
Apixaban is recommended over placebo for cancer-associated thrombosis, with a starting dose of 10 mg twice daily for the first 7 days, followed by 5 mg twice daily for at least 6 months. This recommendation is based on the most recent and highest quality study, which found that apixaban significantly reduces the risk of recurrent VTE in cancer patients compared to placebo, while maintaining an acceptable bleeding risk profile 1. The study, published in The Lancet Oncology in 2022, upgraded the recommendation for direct oral anticoagulants, including apixaban, from 1B to 1A, indicating a strong recommendation with high-certainty evidence.
Key Considerations
- Apixaban works by selectively inhibiting factor Xa, thereby preventing thrombin formation and clot development.
- Unlike warfarin, apixaban does not require routine monitoring and has fewer drug-drug interactions, making it particularly suitable for cancer patients who often take multiple medications.
- However, dose adjustments may be necessary for patients with severe renal impairment, low body weight, or those taking strong CYP3A4 and P-gp inhibitors.
- Regular assessment of bleeding risk is essential, especially in patients with gastrointestinal or genitourinary malignancies who may have a higher bleeding risk, as noted in a study published in Chest in 2021 1.
- The AVERT study, published in the Journal of Thrombosis and Haemostasis in 2019, also found that apixaban significantly reduced VTE rate compared to placebo, with a hazard ratio of 0.41 and a number needed to treat of 17 1.
Bleeding Risk
- The risk of major bleeding with apixaban is increased compared to placebo, but the overall benefit of reducing recurrent VTE outweighs this risk.
- Patients with luminal GI malignancies may be at higher risk of GI major bleeding with edoxaban and rivaroxaban, but apixaban does not appear to be associated with this increased risk 1.
From the Research
Comparison of Apixaban and Placebo in Cancer-Associated Thrombosis
- There are no direct studies comparing apixaban to placebo in cancer-associated thrombosis, as the provided evidence compares apixaban to low molecular weight heparin (LMWH) or other anticoagulants 2, 3, 4, 5, 6.
- However, the studies suggest that apixaban may be a preferable treatment option for cancer-associated venous thromboembolism (CA-VTE) due to its lower risk of severe bleeding and reduced recurrence of pulmonary embolism (PE) compared to LMWH 2, 3, 5.
- A study found that extended treatment with apixaban was associated with lower rates of recurrent VTE, major bleeding, and clinically relevant non-major bleeding compared to LMWH in adults with cancer-associated VTE 5.
- Another study 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, and the reduced dose led to a lower incidence of clinically relevant bleeding complications 6.
Efficacy and Safety of Apixaban
- Apixaban has been shown to be effective in preventing recurrent thrombosis in cancer-associated VTE, with a lower risk of major bleeding compared to LMWH 2, 3, 5.
- However, there are still concerns regarding the bleeding associated with apixaban therapy, and regarding the optimal management of these bleeding emergencies 4.
- The pharmacologic profile of apixaban may prefer this agent for the treatment of CA-VTE, but additional research is required to validate these conclusions and evaluate its long-term efficacy and safety 2, 4.