A meta-analysis was performed to evaluate if anticoagulation with DOACs resulted in increased risk of intracranial hemorrhage (ICH) in comparison to low molecular weight heparin (LMWH) in treating venous thromboembolic events (VTE) in patients with primary or metastatic brain tumors.

Patients with malignant brain tumors have a 20 to 30% incidence of venous thromboembolism. ICH is a dreaded complication with anticoagulant use. Phase III clinical trials have established the safety of DOACs in treating VTE in systemic cancers. However, there is a dearth of literature evaluating the safety of DOAC use in brain tumor patients with VTE as phase III trials on DOACs in cancer patients have either excluded or have very small number of patients with brain tumors.

A literature search on Pubmed was obtained using the search terms: ((direct oral anticoagulant OR oral anticoagulant) AND (cancer)) AND (clinical trial) to search all studies using DOACs in cancer. (((Direct oral anticoagulants) OR (anticoagulants)) OR (DOAC)) AND (("brain tumors") OR glioblastoma OR glioma OR ("brain metastases")) was also searched. A random effect model using inverse variance weighting for meta-analysis was conducted to summarize the data and assess the difference in ICH between DOAC and LMWH. The results were expressed as odds ratio (OR) with 95% confidence intervals (95%CI); The I² statistic was used to evaluate the heterogeneity of the pooled data.

Five studies with a total of 713 subjects (265 DOAC subjects and 448 LMWH subjects) were included. The meta-analysis revealed that brain tumor patients treated with DOAC were less likely to experience an event of ICH compared to patients on LMWH (pooled Odds ratio = 0.35, 95%CI = (0.18-0.67), p=0.0014, I² =17%). 

This meta-analysis of available studies shows that DOAC are safer in comparison to LMWH with a lower incidence of ICH in patients with brain tumors.