Modified vs Full Lead-in Dose Apixaban and Rivaroxaban for Treatment of Acute Venous Thromboembolism

Background: Apixaban and rivaroxaban, direct oral anticoagulants (DOACs) used for acute venous thromboembolism (VTE) treatment, require higher dose lead-in periods of 7 days and 21 days, respectively. The optimal lead-in duration for patients receiving more than 48 hours of parenteral anticoagulation (AC) is unclear. In addition, guidelines lack recommendations for high bleed-risk patients who might benefit from a shortened lead-in. Objective: This study aimed to evaluate the effectiveness and safety of a modified lead-in strategy, where parenteral AC counts toward shortening or eliminating the DOAC lead-in period, compared to a full lead-in strategy, where a 7-day apixaban or 21-day rivaroxaban lead-in is prescribed irrespective of parenteral AC received. Methods: A retrospective cohort study analyzed patients diagnosed with an acute VTE during hospitalization. Patients were grouped based on a modified versus full lead-in strategy. Primary outcomes of recurrent VTE (rVTE) and bleeding were evaluated at 90 days. Results: Of 101 included patients, 47 were in the modified lead-in group and 54 in the full lead-in group. Patients in the modified lead-in group had a higher risk of bleeding at baseline. Recurrent VTE occurred in 4 patients in the modified lead-in group, compared to 2 patients in the full lead-in group (9% vs 4%; P = .4129). Bleeding occurred in 10 patients in the modified lead-in group, compared to 3 patients in the full lead-in group (21% vs 6%; P = .0167). Conclusion and Relevance: No significant difference in rVTE was observed between groups. The modified lead-in group had a higher incidence of bleeding, possibly reflecting greater baseline risk and clinical complexity rather than the modification itself. Modified lead-in strategies may be reasonable in select patients, particularly those at high risk for bleeding; however, larger studies are needed to confirm safety and efficacy.