Full- versus Reduced-Dose Direct Oral Anticoagulants for Extended Treatment of Cancer-Associated Thrombosis: A Multicenter Retrospective Cohort Study

Abstract Extended anticoagulation is recommended in subjects with cancer-associated thrombosis (CT). The API-CT trial showed that reduced-dose apixaban is noninferior to full dose for preventing recurrent venous thromboembolism (VTE), but the generalizability of these findings to real-world populations remains to be determined. We conducted a multicenter retrospective cohort study including patients with CT receiving extended direct oral anticoagulants (DOACs) at full or reduced dose, after at least 6 months of anticoagulation. The primary efficacy outcome was recurrent VTE. The primary safety outcome was major bleeding (MB) and clinically relevant nonmajor bleeding (CRNMB). A total of 603 patients were included, of whom 381 (63.2%) received reduced-dose and 222 (36.8%) full-dose DOACs. During a median follow-up of 335 days, recurrent VTE occurred in 3.9% of patients in the reduced-dose and 2.7% in the full-dose group (p = 0.4). MB occurred in 1.0 and 0.9% (p = 0.9) and CRNMB in 4.7 and 5.4% (p = 0.7), respectively. In adjusted analyses, reduced-dose DOACs were associated with a nonsignificant increase in VTE recurrence (hazard ratio: 1.4, 95% confidence interval: 0.5–3.7), with no differences in bleeding outcomes. In this multicenter real-world cohort, reduced-dose DOACs were associated with low rates of recurrent VTE and bleeding, comparable to those observed with full-dose regimens. These findings suggest that reduced-dose anticoagulation may be a feasible option in selected patients with CT requiring extended treatment, supporting individualized decision-making. Further studies are needed to better define optimal dose selection in this setting.