Real-World Evaluation of the Safety and Effectiveness of Apixaban & Rivaroxaban Lead-in Dosing Compared to Parenteral Lead-in Dosing in the Treatment of Venous Thromboembolism: A Multi-Center Retrospective Cohort Study.

Background: Although parenteral anticoagulation lead-in is not recommended with apixaban and rivaroxaban, parenteral anticoagulation is often used to replace apixaban or rivaroxaban lead-in doses for the initial phase treatment of VTE. Thus, our study compares the safety and effectiveness of lead-in parenteral anticoagulation to lead-in apixaban or rivaroxaban in patients who received apixaban or rivaroxaban for VTE treatment.

Methods: A multi-center retrospective cohort study included adult patients (aged ≥ 18 years) admitted to the hospital with acute VTE and treated with either apixaban or rivaroxaban. Patients were grouped depending on the lead-in anticoagulation received for initial VTE treatment into the "Direct oral anticoagulation (DOAC) lead-in" group if patients received an appropriate lead-in dose of apixaban and rivaroxaban and patients who received parenteral lead-in the "parenteral lead-in" group.

Results: A total of 389 patients were included; the DOAC lead-in group included 296 patients, whereas 93 patients were in the parenteral lead-in group. VTE recurrence (rVTE) during hospitalization and within 30 days was numerically higher in the parenteral lead-in group compared to the DOAC lead-in group (3.3% vs 0.6%; =0.09 and 1.1% vs 0.7%; =0.560), with a significantly higher number of patients with rVTE at 90 days (5.4% vs 1.4%; =0.039). However, none of the patient's characteristics were significantly associated with the incidence of rVTE. In addition, the major bleeding rate during hospitalization was significantly higher among the parenteral lead-in group than in the DOAC lead-in group (14.0% vs 3.7%; <0.001).

Conclusion: Parenteral anticoagulation lead-in before starting maintenance of apixaban and rivaroxaban showed a significantly higher risk of bleeding and a trend toward higher VTE recurrence than the DOAC lead-in. This study adds to the evidence supporting the utilization of the DOAC lead-in regimen in treating patients with VTE. Still, larger studies with robust designs are needed to confirm these findings.