Risk of intracranial hemorrhage with DOACs vs LMWH in patients with cancer-associated thrombosis and brain metastases.

2034 Background: Intracranial hemorrhage (ICH) is a major and often devastating complication in patients with brain metastases requiring therapeutic anticoagulation for cancer-associated thromboembolism (CAT). While direct oral anticoagulants (DOACs) provide a convenient alternative to low-molecular-weight heparin (LMWH), their safety in this population remains unclear. Comparing ICH risk between DOACs and LMWH is crucial for optimizing anticoagulation in these high-risk patients. Methods: This retrospective cohort study utilized TriNetX, a multi-institutional database, to analyze adults with solid tumors who developed CAT within six months of brain metastasis diagnosis. Patients receiving therapeutic-dose DOACs (apixaban, rivaroxaban, edoxaban) or LMWH within ten days of venous thromboembolism diagnosis were compared. 1:1 propensity score matching for over 50 covariates, including age, sex, and cancer type (Table 1). We assessed ICH incidence, bleeding events, ICU admissions, and all-cause mortality using Kaplan-Meier survival analysis and Cox proportional hazards models. Subgroup analyses examined ICH risk by cancer type. Results: After matching, 4,275 patients were included in each group. DOACs were associated with a statistically significant lower risk of ICH (HR 0.855, 95% CI 0.731-0.999, p=0.049). Additionally, significantly lower rates of ICU admission (16.7% vs. 20.3%; p<0.001) and all-cause mortality at 12 months (42.4% vs. 48.9%; p<0.001) were observed in the DOAC group. Subgroup analyses showed a trend toward lower ICH with DOACs in lung cancer (5.9% vs. 6.1%, p=0.726), melanoma (13.7% vs. 15.9%, p=0.432), and renal cell carcinoma (5.7% vs. 9.0%, p=0.103), but these differences were not statistically significant. No significant differences were found for breast (3.6% vs. 4.5%, p=0.375) or colorectal cancer (4.0% vs. 5.4%, p=0.331). Conclusions: DOACs were associated with significantly lower ICH, ICU admission, and mortality compared to LMWH in patients with brain metastases requiring anticoagulation, supporting their role as a viable and well-tolerated alternative. While subgroup analyses did not show significant differences in ICH risk by cancer type, the overall findings indicate a favorable profile for DOACs. These results highlight the need for individualized anticoagulation strategies and warrant further prospective validation. Baseline characteristics after matching. Characteristic DOAC (n=4275) LMWH (n=4275) Age (years), mean ± SD 63.4 ± 11.9 63.5 ± 11.9 Female, n (%) 1969 (46.1%) 1958 (45.8%) Lung Cancer, n (%) 2218 (51.9%) 2229 (52.1%) Breast Cancer, n (%) 692 (16.2%) 672 (15.7%) Melanoma, n (%) 280 (6.5%) 279 (6.5%) Renal Cell, n (%) 241 (5.6%) 244 (5.7%) Colorectal, n (%) 408 (9.5%) 413 (9.6%)