Comment on model-based meta-analysis to evaluate optimal doses of direct oral factor Xa inhibitors in atrial fibrillation patients

In a recent issue of Blood Advances, Yoshioka et al 1 performed a model-based meta-analysis (MBMA) to evaluate the optimal dose of rivaroxaban, apixaban, and edoxaban in patients with atrial fibrillation (AF). To develop the model, they used reported population pharmacokinetic (PK) and pharmacodynamic models to estimate time profiles of changes in the prothrombin time (PT) in 5 randomized controlled trials (RCTs) that evaluated the efficacy and safety of oral factor Xa (FXa) inhibitors in AF patients. After assay normalization, the authors calculated the model-based relationships between the simulated PT ratio profiles and the rates of ischemic stroke or systemic embolism and major bleeding, and used this information to determine the dose of each oral FXa inhibitor that would achieve minimal simulated mortality.