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Clinical evaluation of laboratory methods to monitor exposure of rivaroxaban at trough and peak in patients with atrial fibrillation

PURPOSE:

The one-dose daily regime of rivaroxaban could cause a pronounced variability in concentration and effect of which a deeper knowledge is warranted. This study aimed to evaluate the typical exposure range and effect of the direct factor Xa (FXa)-inhibitor rivaroxaban in a cohort of well-characterized patients with atrial fibrillation (AF).

METHODS:

Seventy-one AF patients (72 ± 8 years, 55 % men) were treated with rivaroxaban 15 mg/20 mg (n = 10/61) OD. Trough (n = 71) and peak (n = 30) plasma concentrations determined by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) were compared to the coagulation assays anti-FXa for rivaroxaban, prothrombin time-international normalized ratio (PT-INR) (venous samples and point-of-care assay (POC) CoaguChek XS Pro), and aPTT.

RESULTS:

Median rivaroxaban plasma concentrations by LC-MS/MS were 34 (range 5-84) and 233 ng/ml (range 120-375) at trough and peak, respectively. A strong correlation between LC-MS/MS and the anti-FXa assay was found (p < 0.001) for both trough (r (2) = 0.92) and peak (r (2) = 0.91) samples. PT-INR results from the POC assay, but not from the conventional PT assay, correlated significantly with LC-MS/MS in peak samples exclusively (r (2) = 0.41, p < 0.001).

CONCLUSIONS:

In "real-life" AF patients treated with rivaroxaban, we observed a pronounced variability in plasma concentrations at trough and to a lesser extent at peak measured by LC-MS/MS. The anti-FXa assay performed well upon rivaroxaban levels in a normal exposure range, although LC-MS/MS remains the only method that covers the whole concentration range with accuracy. Interestingly, the POC assay for PT-INR could be useful to indicate high exposure to rivaroxaban in emergency situations although further validation is required.

Related Products

Cat.No. Product Name Information
S3002 Rivaroxaban Rivaroxaban is a direct inhibitor of Factor Xa with Ki and IC50 of 0.4 nM and 0.7 nM in cell-free assays, respectively. It is selective for human factor Xa, for which it has >10 000-fold greater selectivity than for other biologically relevant serine proteases (IC50 >20 μM).

Related Targets

Factor Xa