Rethinking lead-in strategies: evaluation of full vs. reduced dose factor Xa inhibitors in acute VTE

Oral factor Xa inhibitors are preferred treatments for venous thromboembolism (VTE). While apixaban and rivaroxaban require an initial lead-in period, clinicians may reduce the period if patients have received prior therapeutic parenteral anticoagulation, although supporting evidence is limited. The purpose of this study is to evaluate bleeding and thrombotic events associated with reducing factor Xa inhibitor lead-in duration in patients who have received prior parenteral anticoagulation. This multicenter retrospective cohort study was conducted across 29 hospitals and included adult patients hospitalized with a new diagnosis of VTE who received at least 24 h of therapeutic parenteral anticoagulation before starting apixaban or rivaroxaban. Patients with active bleeding on admission, anticoagulation prior to admission, antiphospholipid syndrome, severe liver disease, or contraindicated medications were excluded. The primary outcome was time to VTE recurrence within six months. Cox proportional hazard model was used to control for potential confounding factors and a sensitivity analysis was performed using propensity matching. Among 1,424 patients included, 1,068 received a full lead-in and 356 a reduced lead-in regimen. No significant difference in time to recurrent VTE (HR 0.53; 95% CI, 0.20-1.37;p = 0.19) or major bleeding (HR 0.69; 95% CI, 0.31-1.56;p = 0.45) was observed after controlling for confounding factors. No difference in recurrent VTE and major bleeding persisted after propensity matching. Among patients transitioning from parenteral anticoagulation to oral factor Xa inhibitors, a reduced lead-in duration was not associated with increased VTE recurrence or major bleeding.