Exploratory Study On Clinical Monitoring Indicators Of Direct Oral Anticoagulant Therapy In Patients With Acute Pulmonary Embolism

Background:Rivaroxaban is widely used in the treatment of acute pulmonary embolism,but current guidelines and product labeling do not provide recommended doses for patients aged 75 and older,nor do they specify methods for drug-specific monitoring.Therefore,it is necessary to identify appropriate indicators for monitoring the anticoagulant effect of rivaroxaban in order to guide individualized and precise treatment.Methods:Correlations between blood drug concentrations and coagulation parameters were analyzed in healthy subjects and patients with acute pulmonary embolism who received different doses of oral rivaroxaban at different time intervals.Subgroup analyses were performed in pulmonary embolism patients based on age,renal function,concomitant medication,and clinical outcomes.The aim was to investigate whether commonly used coagulation-related tests could serve as evaluation indicators for the anticoagulant effect or bleeding risk of rivaroxaban.Results:In healthy subjects,there was no twofold relationship between plasma drug concentrations after taking 20 mg and 10 mg of rivaroxaban at the same time,and the peak concentration was significantly higher with 20 mg compared to 10 mg(p<0.05).In patients with pulmonary embolism,there was no twofold relationship between plasma drug concentrations after taking 20 mg and 10 mg of rivaroxaban at the same time,and there was no statistically significant difference in peak concentration(p>0.05).After 24 hours of administration,plasma drug concentrations did not decrease to zero in both healthy subjects and patients with pulmonary embolism.In both healthy subjects and patients with pulmonary embolism,the trends in changes of APTT,PT,and FXa inhibition were consistent with plasma drug concentrations,and the results of anti-Xa chromogenic assay showed a strong correlation with liquid chromatography-tandem mass spectrometry(R2>0.800,p<0.05).Under the same dose of medication,plasma drug concentrations were higher in patients aged 75 and older compared to those under 75 after 4 hours of administration and onwards,but the difference was not statistically significant(p>0.05).Conclusions:The plasma drug concentration showed good agreement with PT and APTT during the peak concentration range.There was a strong positive correlation between the results of the anti-Xa chromogenic assay and the LC-MS/MS method.Safety assessment and monitoring of drug use in special populations are necessary in the Asian population.The plasma peak concentration as a monitoring indicator for bleeding risk still requires further validation.