Safety of DOACs vs. LMWH in brain tumor-associated thrombosis

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Created On: 04/02/2026

Patients diagnosed with primary or metastatic brain tumors are at substantially higher risk of arterial and venous thromboembolism (VTE).

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Key take away

In brain tumor–associated thrombosis, DOACs demonstrate superior intracranial safety over LMWH.

Background

Patients diagnosed with primary or metastatic brain tumors are at substantially higher risk of arterial and venous thromboembolism (VTE). Anticoagulation decisions in this population remain challenging due to the competing concern of intracranial hemorrhage (ICH). As a result, real-world clinical practice varies widely regarding the choice of anticoagulant therapy.

The aim of this meta-analysis was to evaluate whether direct oral anticoagulants (DOAC) therapy is associated with a lower risk of intracranial bleeding compared with low-molecular-weight heparin (LMWH) in brain tumors.

Method

A systematic literature search was carried out in Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and Web of Science. Eligible studies included randomized controlled trials and observational cohort studies involving adult patients (≥18 years) with primary or metastatic brain tumors receiving therapeutic-dose DOACs (apixaban, rivaroxaban, edoxaban, betrixaban, or dabigatran) or LMWH (enoxaparin, dalteparin, nadroparin, or tinzaparin).

Studies evaluating prophylactic anticoagulation or non–brain tumor populations were excluded.
Using restricted random-effects model, pooled risk ratios (RRs) along with 95% confidence intervals were checked. Statistical heterogeneity (I²), publication bias, subgroup analyses (study quality, tumor type, and follow-up duration), and sensitivity assessment were conducted.

Result

From 762 screened records, 10 retrospective cohort studies encompassing 1,572 patients were included (645 DOAC-treated and 895 LMWH-treated patients). The average or median patient age was between 60.4 and 67 years among those receiving DOACs, compared with 53 to 64 years in the LMWH cohort. The duration of follow-up across studies varied from 3 to 12 months. Overall, those receiving DOACs experienced a markedly lower incidence of ICH compared with those treated with LMWH (RR = 0.50; I² = 49.5%).

The benefit was most pronounced in studies with 3-month follow-up, demonstrating a substantial reduction in ICH risk (RR = 0.23; I² < 0.01%). Subgroup analyses revealed a robust reduction in intracranial bleeding among patients with primary brain tumors receiving DOACs (5 studies; RR = 0.20). In contrast, no vital difference in ICH risk was noted between DOACs and LMWH in metastatic brain tumors (5 studies; RR = 0.86). Sensitivity analyses confirmed the stability of results, and cumulative meta-analysis exhibited consistent effect estimates with narrowing confidence intervals over time. Egger’s and Begg’s tests illustrated no evidence of publication bias.

Conclusion

DOACs were associated with a lower risk of ICH than LMWH in anticoagulated patients with brain tumors, particularly those with primary brain malignancies. These findings support the usage of DOACs as a safer anticoagulation option for cancer-related arterial and VTE in carefully selected patients.