Direct oral anticoagulants versus low-molecular-weight heparin in patients with liver metastases and cancer-associated thrombosis: A multi-center real-world analysis.

11179 Background: Patients with liver metastases are at high risk for cancer-associated thrombosis (CAT) and require therapeutic anticoagulation. Although direct oral anticoagulants (DOACs) are increasingly used, their safety relative to low-molecular-weight heparin (LMWH) in this high-risk population, particularly regarding gastrointestinal (GI) bleeding, remains uncertain. Methods: We conducted a retrospective, federated cohort study using the TriNetX Global Collaborative Network, including adult patients with liver metastases and CAT who initiated a DOAC or LMWH within 10 days of CAT diagnosis. The index date was defined as the first qualifying anticoagulant exposure. Propensity score matching was performed to balance measured demographics, comorbidities, and concomitant medications, yielding 19,380 patients per cohort. Outcomes were assessed from 1 to 365 days after the index date and included GI bleeding, thrombotic recurrence by DVT/PE or stroke, intensive care unit (ICU) admission, and all-cause mortality. GI bleeding was identified using diagnosis-based coding algorithms, with exclusion of patients who had GI bleeding prior to anticoagulation initiation. Risk estimates were calculated and time-to-event analyses. Results: GI bleeding occurred more frequently among patients treated with DOACs compared with LMWH (9.7% vs 8.3%; hazard ratio [HR] 1.11, 95% CI 1.02–1.19). Thrombotic recurrence was common in both groups (61.4% with DOACs vs 60.0% with LMWH); however, time-to-event analysis demonstrated a modestly lower hazard of recurrence among DOAC-treated patients (HR 0.94, 95% CI 0.92-0.97). ICU admission was infrequent but occurred more often in the DOAC cohort (0.6% vs 0.3%; HR 1.80, 95% CI 1.33–2.46). DOAC use was associated with significantly lower all-cause mortality compared with LMWH (50.8% vs 55.7%; HR 0.84, 95% CI 0.82–0.86). Conclusions: In patients with liver metastases and CAT, DOAC therapy was associated with a modestly increased risk of GI bleeding but improved overall survival compared with LMWH. Given the small absolute differences in bleeding risk and the potential for residual confounding from unmeasured factors such as cancer burden, performance status, life expectancy, and hospice referral, these findings may support clinical equipoise between anticoagulation strategies. Individualized treatment decisions remain essential in this vulnerable population. Clinical outcomes in propensity-score matched patients with liver metastasis and cancer associated thrombosis. Outcome DOAC (n=19,380) LMWH (n=19,380) HR CI GI bleeding 9.7% 8.3% 1.11 1.02-1.19 Thromboembolic recurrence 61.4% 60.0% 0.94 0.92-0.97 ICU admission 0.6% 0.3% 1.80 1.33-2.46 All-cause mortality 50.8% 55.7% 0.84 0.82-0.86