Neurology. 2025 Oct 21;105(8):e214140. doi: 10.1212/WNL.0000000000214140. Epub 2025 Sep 15.
ABSTRACT
BACKGROUND AND OBJECTIVES: Patients with brain tumors face an increased risk of arterial and venous thromboembolic events. However, owing to risk of intracranial hemorrhage (ICH), clinician practice patterns vary on preference for anticoagulation treatment. This meta-analysis evaluates the safety of direct oral anticoagulants (DOACs) vs low-molecular-weight heparin (LMWH) on the development of ICH in patients with brain tumor.
METHODS: We searched MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (January 2010-June 2025) for randomized-controlled trials or cohort studies enrolling adults (age ≥18 years) with primary or metastatic brain tumors receiving therapeutic DOACs (apixaban, rivaroxaban, edoxaban, betrixaban, and dabigatran) vs LMWH (enoxaparin, dalteparin, nadroparin, and tinzaparin). Studies limited to prophylactic dosing or non-brain tumor patients were excluded. Pooled risk ratios (RRs) with 95% CIs were calculated using a restricted random-effects model. Heterogeneity (I2) and bias were evaluated, with prespecified subgroups (tumor type, follow-up duration, and study quality) and sensitivity analyses. The study protocol was registered on PROSPERO (CRD42025635334).
RESULTS: Among 762 publications identified, 10 retrospective cohort studies (1,572 patients: 645 DOAC, 895 LMWH) were included. Patients’ mean or median age ranged 60.4-67 years (DOAC) vs 53-64 years (LMWH), with follow-up durations ranging from 3 to 12 months. Patients with primary or metastatic brain tumors receiving DOACs had a statistically significantly lower risk of any ICH compared with LMWH (RR = 0.50, 95% CI 0.29-0.87; p = 0.01, I2 = 49.50%). Reduction was more pronounced in 3 studies with three-month follow-up (RR = 0.23, 95% CI 0.09-0.57; p < 0.01, I2 < 0.01%). Stratified analyses showed reduced ICH risk with DOACs in primary brain tumors (5 studies, RR = 0.20, 95% CI 0.08-0.54; p < 0.01, I2 < 0.01%) but not in metastatic brain tumors (5 studies, RR = 0.86, 95% CI 0.44-1.68; p = 0.66, I2 = 36.04%). Leave-one-out analyses confirmed robustness, and cumulative meta-analysis demonstrated stable estimates with narrowing CIs. Egger (p = 0.19) and Begg (p = 0.59) tests showed no statistical evidence of publication bias.
DISCUSSION: In the current meta-analysis, DOACs were associated with significantly lower ICH risk than LMWH in patients with anticoagulated brain tumor, particularly those with primary brain tumors. Findings support DOACs as a safe anticoagulant in arterial and venous thromboembolism. Given observational designs with inherent confounding, findings warrant cautious interpretation.
PMID:40953341 | DOI:10.1212/WNL.0000000000214140
