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Comparison of Peak and trough Concentrations of Dabigatran, Rivaroxaban and Apixaban with the Published Expected Values in Patients with Non Valvular Atrial Fibrillation

Background : Direct oral anticoagulants (DOACs), dabigatran, rivaroxaban and apixaban, have been increasingly used for the prevention and treatment of thromboembolic diseases in recent years. However, peak and trough concentrations of these DOACs in certain clinical indications are still insufficiently investigated. Aims : The aim was to assess both peak and trough plasma concentrations of all three DOACs in patients treated for non valvular atrial fibrillation (NVAF) and to compare our own results with the first published expected values. Methods : The study included plasma samples from patients treated for NVAF and taking dabigatran (N=37), rivaroxaban (N=28) and apixaban (N=36). Blood samples were taken on the same day to obtain both trough (immediately prior the next drug dose) and peak (two hours after drug administration) DOACs concentrations. Rivaroxaban and apixaban concentrations were measured using chromogenic anti- FXa assay (Innovance anti- FXa, Siemens Healthineers, Germany) calibrated with specific calibrators for rivaroxaban and apixaban (Hyphen BioMed, France). Dabigatran was measured using commercial chromogenic method (Innovance DTI assay, Siemens Healthineers, Germany). All coagulation assays were performed on Behring Coagulation System XP (BCSXP) analyser (Siemens Healthineers, Germany). Statistical analysis was done using Mann- Whitney test by MedCalc Statistical Software version 11.5.1. The study was funded as an integral part of the Croatian Science Foundation research project IP- 2016- 06- 8208. Results : Concentrations for all three DOACs ranged as follows: dabigatran (peak 14- 415 ng/mL ; trough 0- 237 ng/mL) ; rivaroxaban (peak 90- 417 ng/mL ; trough 1- 188 ng/mL) and apixaban (peak 60- 385 ng/ mL ; trough 13- 221 ng/mL) with statistically significant differences between peak and trough concentrations (P< 0.001) for all three DOACs (Table 1). Peak and trough concentrations obtained in our study for all three DOACs conformed with published expected values for most samples analyzed (Table 1). Conclusions : The study showed a good agreement of both peak and trough concentrations for dabigatran, rivaroxaban and apixaban with the published expected values in NVAF patients.

dabigatran, rivaroxaban, apixaban, concentration, NVAF

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