Risk of Intracranial Hemorrhage with Direct Oral Anticoagulants (DOACs) Versus Low Molecular Weight Heparin (LMWH) in Primary and Secondary Brain Cancers: An up-to-Date Meta-Analysis of Comparative Studies

Abstract

Introduction Patients with brain tumors, primary or metastatic, are at high risk for thromboembolic events and anticoagulant-associated bleeding. LMWH has been the standard treatment for many years. Recently, DOACs are more frequently used in cancer patients. However, such patient populations have been under-represented in anticoagulation trials. As such, there continues to be concerns regarding their safety in patients with primary and metastatic brain cancers especially with respect to intracranial hemorrhages (ICH). There are no trials in brain cancers comparing the safety of DOACs to LMWH in a head-to-head manner. This meta-analysis was conducted to compare the relative risk (RR) of ICH of DOACs to that of LMWH in patients with brain cancers. Methods A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of primary brain cancers (PBC) or metastatic brain cancers (MBC), comparative studies using anticoagulation with LMWH versus DOACs, and studies that reported the incidence of ICH. A meta-analysis using the fixed effects and random effects models was conducted. Results Four retrospective comparative studies with a total of 488 patients were included. Three studies reported on ICH incidence of DOACs versus LMWH in PBC and MBC separately and one reported on ICH incidence in MBC only. DOACs were found to have significantly lower RR of all types of ICH in patients with PBC (RR=0.18, 95%CI 0.05-0.62) and a borderline significant lower RR in MBC (RR=0.66, 95%CI 0.41-1.08) than LMWH. However, there was no significant difference between DOACs and LMWH with respect to major ICH in patients with MBC. Conclusions This is the first meta-analysis to show that DOACs is associated with lower relative risk of all ICH compared to LMWH in patients with primary and metastatic brain cancers. In the absence of randomized clinical trials, it represents the most compelling data supporting the use of DOACs to treat thromboembolic events in these patient populations.