Anticoagulant monitoring of rivaroxaban by chromogenic anti-Xa assays and UHPLC-MS/MS in patients with atrial fibrillation

Abstract Background: Monitoring the level of anticoagulation by rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) is valuable in clinical practice. Our study aimed to measure the plasma levels of rivaroxaban both by chromogenic anti-Xa assays and ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) in Chinese patients with NVAF, and compare with the expected drug levels. Materials and methods: A prospective clinical study was conducted to include NVAF patients taking rivaroxaban. Rivaroxaban levels were determined using UHPLC-MS/MS and chromogenic anti-Xa assays (Biophen DiXal and Zhenyuan anti-Xa). The correlation and agreement among measurements by different assays were evaluated. The rivaroxaban levels in Chinese patients were also compared with the expected drug levels, which were estimated from previous clinical trials and widely accepted. Results: A total of 243 plasma samples were collected from 182 patients. Results measured using the two chromogenic anti-Xa assays were both linearly correlated with those measured using UHPLC-MS/MS, especially in the range of 50–200 ng/mL, but the concentrations determined using anti-Xa assays were systematically underestimated. Rivaroxaban levels measured by either UHPLC-MS/MS or chromogenic anti-Xa assays were both larger than the expected ranges. There was no difference in the distribution of concentration whether the patients took an appropriate dose or not. However, for Chinese patients with an inappropriate lower dose, trough concentrations were less likely to exceed the expected concentration ranges.Conclusion: Rivaroxaban concentration in patients with NVAF were highly variable compared to the expected ranges estimated from clinical trials, whether measured by UHPLC-MS/MS or chromogenic anti-Xa assays. Chinese patients taking an appropriate rivaroxaban dose are more likely to obtain a rivaroxaban concentration level higher than expected, independent on the assay used.