Variation in Plasma Levels of Apixaban and Rivaroxaban in Clinical Routine Treatment of Venous Thromboembolism

Abstract

Direct oral anticoagulants (DOACs) apixaban and rivaroxaban are broadly used in the management of venous thromboembolism (VTE). Although not routinely required, measurement of their plasma concentration is advised for an increasing number of indications. Due to the lack of therapeutic ranges, current guidelines recommend reporting DOAC plasma levels together with expected levels from previous pivotal studies. The aim of this study was to assess DOAC level variation in a large VTE patient population. Drug concentrations determined by measurement of the anti-Xa-activity using drug-specific calibrators in citrated plasma samples from patients on rivaroxaban (n = 1471) or apixaban (n = 725) were analyzed. Observed 5th–95th percentile ranges of apixaban peak/trough levels (63–299/13–114 ng/mL for 5 mg, 37–161/7–68 ng/mL for 2.5 mg twice daily) were similar to previously reported mass-spectrometry-based reference data, and 10th–90th percentile ranges of rivaroxaban peak/trough levels (98–367/8–55 ng/mL for 20 mg, 51–211/5–27 ng/mL for 10 mg once daily) were even narrower. Age and drug levels correlated weakly (r ≤ 0.330). Drug levels measured repeatedly in subgroups of patients showed a strong correlation (r ≥ 0.773). In conclusion, anti-Xa-activity-based measurement of apixaban and rivaroxaban yields reliable results. However, the paucity of levels off-range underlines the need for evidence-based thresholds to better assist clinical decision making.

Stability of Direct Oral Anticoagulants Concentrations in Blood Samples for Accessibility Expansion of Chromogenic Assays

“…Nonetheless, studies that are directed to determine intra- and inter-individual variation for DOACs are lacking, as is common for almost all drugs. Based on the study by Reda et al, inter-individual biological variations for various DOACs exceed 40% at peak and 60% at trough concentrations and intra-individual CV above 20%, so the acceptable CV was set at 20% even though the analytical CV was below 10% [ 30 , 31 , 33 ]. It is essential to take into consideration that the lower concentrations had higher deviations from baseline values in percentages, but clinically, this was not significant, e.g., the sample’s baseline value was 24 ng/mL with 37.5% deviations on the third day, which meant 33 ng/mL ( Table 2 and Table 3 ).…”