Monte Carlo simulation-based optimization of the rivaroxaban regimen for anticoagulation in patients with different classes of renal function
OBJECTIVE To optimize the rivaroxaban dosing regimen for anticoagulation in patients with different renal function levels.METHODS The administration regimen was determined based on the drug instructions for rivaroxaban and the actual medication situation of the patient.The target concentration range and the subsection interval were established using rivaroxaban blood minimum concentration for patients from Hebei General Hospital and reference range of rivaroxaban laboratory monitoring concentration recommended by International Council for Standardization in Hematology.The probability of different dosing regimens in each target concentration range was investigated with Monte Carlo simulation using Oracle Crystal Ball software(V11.1.2.4).RESULTS A total of 97 patients with non-valvular atrial fibrillation were enrolled and the minimum concentration of rivaroxaban was tested 125 times with a median trough concentration of 32.2 ng/mL;a total of 121 patients with venous thrombosis were enrolled and the minimum concentration was tested 159 times with a median minimum concentration of 31.0 ng/mL.The reference range for steady-state minimum concentration in patients with non-valvular atrial fibrillation was 12-137 and 3-153 ng/mL,while the reference range for steady-state minimum concentration in patients with venous thrombosis was 6-239 and 3-224 ng/mL.Monte Carlo simulation results showed that in patients with non-valvular atrial fibrillation,the optimal rivaroxaban dosing regimen for patients with glomerular filtration rate(eGFR)0-30 mL/min was 5 mg once daily;for patients with eGFR＞30-60 mL/min,the optimal dosing regimen was 10-20 mg once daily or 5 mg twice daily;for patients with eGFR＞60-90 mL/min,the optimal dosing regimen was 15-30 mg once daily or 5-10 mg twice daily;for patients with eGFR＞90-120 mL/min,the optimal dosing regimen was 25-30 mg once daily or 5-15 mg twice daily.For patients with venous thrombosis,it is not recommended to use rivaroxaban more than 5 mg once daily for patients with eGFR 0-30 mL/min;the optimal dosing regimens of rivaroxaban were 5 mg once daily for patients with eGFR＞30-60 mL/min,25-30 mg once daily or 5-15 mg twice daily for patients with eGFR＞60-90 mL/min,10-15 mg twice daily for patients with eGFR＞90-120 mL/min.CONCLUSIONS Rivaroxaban should be selected carefully as the anticoagulants for patients with severe renal function impairment.Rivaroxaban possesses a wide reference range in the minimum concentration and considerable individual variability.The dosage and frequency of rivaroxaban can be personalized through the Monte Carlo simulation method,taking into account patients'renal function.
rivaroxabanrenal functionMonte Carlo simulationanticoagulation regimennon-valvular atrial fibrillationvenous thrombosis
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