Peak and Trough Concentration Ranges of Factor Xa Inhibitors for Preventing Thromboembolic Stroke in Korean Patients...

Current guidelines recommend factor IIa- or Xa-specific inhibitors over warfarin analogs for preventing thromboembolic stroke in patients with atrial fibrillation (AF). However, their plasma concentrations in Korean patients are not well understood.

We conducted a single-center laboratory study to determine the distribution ranges of peak and trough concentrations of three factor Xa inhibitors (apixaban, edoxaban, and rivaroxaban) prescribed for preventing strokes in patients with AF. Patients receiving one of these drugs and undergoing blood specimen collection for laboratory tests were screened. Blood specimens were obtained from patients who had adhered to the prescribed drug regimen consistently for at least 1 week. Drug plasma concentrations were measured using heparin liquid-reagent technology-based anti-Xa chromogenic assays.

We selected 459 patients who were taking standard or on-label-reduced doses of apixaban (N=252), edoxaban (N=182), or rivaroxaban (N=25). The 5th-95th percentile ranges of the peak concentrations were 84-414 ng/mL (apixaban), 72-424 ng/mL (edoxaban), and 97-517 ng/mL (rivaroxaban). The respective 5th-95th percentile ranges of the trough concentrations were 44-237 ng/mL, 23-93 ng/mL, and 13-219 ng/mL. Approximately 19.6% (apixaban), 33.3% (edoxaban), and 64.0% (rivaroxaban) of patients in each group had peak concentrations out of the predicted distribution ranges based on pharmacokinetic data. Approximately 7.3%, 52.8%, and 8.3% of patients had trough concentrations out of the predicted distribution ranges.

A considerable proportion of Korean patients with AF taking factor Xa inhibitors may require population-specific reference ranges to guide therapeutic monitoring.