Impact of Apixaban Lead-In Therapy Duration After Parenteral Anticoagulation on Bleeding in Patients Treated for Venous Thromboembolism

<b>Background:</b> Venous thromboembolism (VTE) treatment with apixaban uses a higher 10 mg twice daily regimen for 7 days (lead-in therapy). But, in patients with initial parenteral anticoagulation treatment or those with higher bleeding risk, clinicians may not always adhere to the full 7-day lead-in duration. <b>Methods:</b> This retrospective cohort study included adult patients admitted to the Veterans Affairs Health care System from January 2011 to April 2022, who received at least 24 hours of parenteral anticoagulation followed by lead-in apixaban therapy for VTE. The primary outcome evaluated bleeding among patients treated with shortened lead-in apixaban (study group) compared to the standard 7-day duration (control group). <b>Results:</b> Seventy-eight patients were included in the control and 65 in the study group. Most patients were treated for PE (72%) and received initial treatment with enoxaparin (71%). Duration of parenteral anticoagulation was longer in the study group (3.6 days ± 3.2 vs 2.5 days ± 1.9; <i>P</i> < .01), and length of apixaban lead-in therapy was decreased (4.1 days ± 2.2 vs 7 days; <i>P</i> < .01). The primary outcome of bleeding was higher in the study group (18.5% vs 5.1%; <i>P</i> = .02), with no difference in VTE recurrence. P2Y₁₂ and P-gp inhibitor use, and increased creatinine and age were predictors of bleeding. <b>Conclusion and Relevance:</b> Bleeding events were increased in the study group, and patients with bleeding risk factors may not benefit from apixaban 10 mg twice daily. Larger studies are needed where apixaban lead-in therapy is omitted following parenteral anticoagulation in patients with bleeding risk factors.