What is the risk of bleeding with Apixaban (apixaban) in patients with brain tumors?

From the Guidelines

Apixaban can be used in patients with brain tumors, but the decision requires careful consideration of individual bleeding risk, and the most recent evidence from 2022 suggests that LMWHs or direct oral anticoagulants, such as apixaban, can be used for the treatment of established VTE in patients with a brain tumor 1. For patients with stable brain tumors without recent bleeding, apixaban at standard dosing (5mg twice daily, or 2.5mg twice daily for patients meeting dose reduction criteria) is typically acceptable, as shown in the AVERT study, where apixaban significantly reduced VTE rate (4.2% on apixaban and 10.2% on placebo, hazard ratio [HR] 0.41; 95% CI, 0.26–0.65; p<0.001) 1. However, apixaban should be avoided in patients with active bleeding, recent intracranial hemorrhage, or highly vascular or hemorrhagic brain tumors, as the risk of major bleeding is increased, with a hazard ratio of 2.00 (95% CI, 1.01–3.95; p=0.046) in the AVERT study 1. Some key points to consider when using apixaban in patients with brain tumors include:

• Close monitoring is essential, with regular neurological assessments and imaging as needed.
• The decision to use apixaban should be made through a multidisciplinary approach involving neurology, oncology, and hematology specialists.
• The benefit of preventing thromboembolism must be weighed against the risk of intracranial bleeding, as apixaban works by inhibiting Factor Xa in the coagulation cascade, which prevents thrombin formation and clot development, but also increases bleeding risk, particularly in patients with lesions that may have compromised vascular integrity, such as brain tumors 1.
• Alternative anticoagulation strategies or mechanical prophylaxis may be considered for very high-risk patients, as suggested by the 2022 ITAC guidelines, which recommend the use of LMWHs or direct oral anticoagulants for the treatment of established VTE in patients with a brain tumor (grade 2A) 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Brain Tumors and Risk of Bleeding with Apixaban

• The risk of bleeding with apixaban in patients with brain tumors is a concern due to the potential for intracranial hemorrhage 2, 3.
• Studies have shown that patients with primary or metastatic brain tumors are at increased risk of developing venous thromboses, and the potential benefit of therapeutic anticoagulation must be weighed against the risk of intracranial hemorrhage 2.
• The risk of spontaneous bleeding is acceptable and not further increased by careful therapeutic anticoagulation with low molecular weight heparin or direct oral anticoagulants, such as apixaban, in most patients with primary or treated metastatic brain tumors 2.
• However, patients with brain metastasis from certain types of cancer, such as melanoma, renal cell carcinoma, choriocarcinoma, thyroid carcinoma, and hepatocellular carcinoma, have a higher tendency to bleed spontaneously and may require alternative strategies such as inferior vena cava filter placement 2.
• A study comparing the efficacy and safety of apixaban with low-molecular weight heparin in patients with active malignancy and acute deep venous thrombosis found no significant difference in major bleeding, recurrent deep venous thrombosis, or minor bleeding between the two groups 4.
• The safety profile of therapeutic anticoagulation with apixaban in patients with brain tumors is still being studied, and more research is needed to fully understand the risks and benefits 3, 4.

Types of Brain Tumors and Bleeding Risk

• Glioblastoma is the most common and aggressive malignant primary brain tumor, and patients with this type of tumor may be at higher risk of bleeding with apixaban 5, 6.
• Meningiomas are typically benign and may not be associated with an increased risk of bleeding with apixaban 6.
• Metastatic brain tumors may be associated with a higher risk of bleeding with apixaban, particularly if the primary cancer is a type that is prone to bleeding, such as melanoma or renal cell carcinoma 2, 3.

Management of Brain Tumors and Anticoagulation

• The management of brain tumors and anticoagulation is complex and requires a multidisciplinary approach, including neurosurgery, radiation oncology, and medical oncology 6.
• Patients with brain tumors who require anticoagulation should be carefully evaluated for their individual risk of bleeding and thrombosis, and alternative strategies such as inferior vena cava filter placement may be considered in certain cases 2, 4.