Reduced Versus Full Lead-In Apixaban or Rivaroxaban in Acute Venous Thromboembolism: A Systematic Review

BackgroundDirect oral anticoagulants (DOACs) are recommended as first-line treatment for acute venous thromboembolism (VTE). The recommended regimen of apixaban and rivaroxaban requires a higher-intensity lead-in phase. However, clinicians may use reduced lead-in strategies due to concerns regarding bleeding risk, planned procedures, or prior parenteral anticoagulation. Recent evidence indicates that reduced lead-in dosing may provide comparable clinical outcomes compared to the recommended full lead-in dosing.MethodsIn this study, recent observational studies comparing reduced versus full lead-in apixaban or rivaroxaban therapy in acute VTE were systematically synthesized. Eligible studies included those involving adults treated with apixaban or rivaroxaban in which the lead-in duration was compared. Outcomes assessed included recurrent VTE, bleeding, and mortality.ResultsNine studies were included in this systematic review; reduced lead-in therapy did not increase VTE recurrence compared with full lead-in regimens. In addition, in these studies, no significant difference was found in major bleeding, clinically relevant non-major bleeding, and mortality across all lead-in strategies.ConclusionEvidence demonstrates that reduced lead-in therapy may be both safe and effective in selected patients, particularly those previously treated with therapeutic parenteral anticoagulation. However, current evidence remains observational and heterogeneous. A target trial emulation is required to define optimal lead-in duration and guide patient-specific dosing strategies.