Key result
Apixaban 5 mg BID was associated with significantly greater overall exposure (AUC 4550 ng h/mL) compared to rivaroxaban (2710 ng h/mL) and edoxaban (1290 ng h/mL) (p < 0.001).
Why the study?
The steady-state pharmacokinetics of different oral direct factor Xa inhibitors had not been compared clinically.
How do the steady-state pharmacokinetic profiles of apixaban, rivaroxaban, and edoxaban compare in clinical practice among patients with nonvalvular atrial fibrillation or venous thromboembolism?
Observational (n=329)
How do the steady-state pharmacokinetic profiles of apixaban, rivaroxaban, and edoxaban compare in clinical practice among patients with nonvalvular atrial fibrillation or venous thromboembolism?
p-value: p=<0.001
Apixaban demonstrates significantly higher overall exposure and trough plasma concentrations compared to rivaroxaban and edoxaban, and higher plasma concentrations may partially predict hemorrhagic events.
Differences in anti-FXa assay sensitivity among FXa inhibitors may affect monitoring; leaves open whether PK variations guide individualized dosing.
BACKGROUND: The anticoagulant actions of oral direct factor Xa (FXa) inhibitors can be inferred from their observed plasma concentrations; however, the steady-state pharmacokinetics (PK) of different FXa inhibitors have not been compared in clinically. METHODS: The sensitivity of the rivaroxaban, apixaban, and edoxaban in the STA-Liquid Anti-FXa assay were compared, and the anti-FXa plasma concentrations were measured for PK assessments. Nonlinear mixed-effects modeling was used to assess population PK in 329 patients with nonvalvular atrial fibrillation or venous thromboembolism. Patients were followed up for an average of 3.6 years. RESULTS: Sensitivity was similar among the three drugs in this assay, which could directly compare plasma concentrations instead of anti-FXa activities. Overall exposure was greatest in 5 mg BID apixaban relative to other drugs (p < 0.001). The geometric mean AUC for the 0 to 24-h interval was 4550 ng h/mL for apixaban, 2710 ng h/mL for 15 mg QD rivaroxaban, and 1290 ng h/mL for 60 mg QD edoxaban. The PKs of 2.5 mg BID apixaban or 15 mg QD rivaroxaban were associated with hemorrhagic events. CONCLUSIONS: Apixaban was associated with greater exposure, higher trough concentrations in plasma compared with rivaroxaban or edoxaban. Furthermore, a higher plasma concentration may partially predict hemorrhagic events.
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Goto et al. (2019) conducted an observational in Nonvalvular atrial fibrillation or venous thromboembolism (n=329). Apixaban vs. Rivaroxaban (15 mg QD) and Edoxaban (60 mg QD) was evaluated on Overall exposure (geometric mean AUC for the 0 to 24-h interval) (p=<0.001). Apixaban 5 mg BID was associated with significantly greater overall exposure (AUC 4550 ng h/mL) compared to rivaroxaban (2710 ng h/mL) and edoxaban (1290 ng h/mL) (p < 0.001).