Fadiea Al-Aieshy1,2, Rickard E Malmström3, Jovan Antovic4, Anton Pohanka5, Yuko Rönquist-Nii5, Maria Berndtsson4, Faris Al-Khalili6, Mika Skeppholm7. 1. Department of Medicine Solna, Karolinska Institutet & Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden. fadiea.al-aieshy@karolinska.se. 2. Clinical Pharmacology, Drug Safety and Evaluation Sector, L7:03, Karolinska University Hospital Solna, -17176, Stockholm, SE, Sweden. fadiea.al-aieshy@karolinska.se. 3. Department of Medicine Solna, Karolinska Institutet & Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden. 4. Department of Coagulation Research, Institute for Molecular Medicine and Surgery, Karolinska Institutet & Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden. 5. Department of Laboratory Medicine Huddinge, Division of Clinical Pharmacology, Karolinska Institutet & Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden. 6. Department of Clinical Sciences, Cardiology Unit, Karolinska Institutet, Danderyds Hospital, Stockholm Heart Center, Stockholm, Sweden. 7. Department of Medicine Solna, Karolinska Institutet & Department of Cardiology, Danderyds Hospital, Stockholm, Sweden.
Abstract
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.
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 AFpatients (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" AFpatients 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.
Entities:
Keywords:
Anti-FXa-assay; LC-MS/MS; NOAC; POC-assay; Rivaroxaban; Therapeutic drug monitoring
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