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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 Publications Customer Product Validation
S3002 Rivaroxaban (BAY 59-7939) Rivaroxaban (BAY 59-7939) 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). (16) (3)

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