Residual rivaroxaban exposure after discontinuation of anticoagulant therapy in patients undergoing cardiac catheterization
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Residual rivaroxaban exposure after discontinuation of anticoagulant therapy in patients undergoing cardiac catheterization. / Wiesen, Martin H J; Blaich, Cornelia; Taubert, Max; Jennissen, Veronika; Streichert, Thomas; Pfister, Roman; Michels, Guido.
in: EUR J CLIN PHARMACOL, Jahrgang 74, Nr. 5, 05.2018, S. 611-618.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Residual rivaroxaban exposure after discontinuation of anticoagulant therapy in patients undergoing cardiac catheterization
AU - Wiesen, Martin H J
AU - Blaich, Cornelia
AU - Taubert, Max
AU - Jennissen, Veronika
AU - Streichert, Thomas
AU - Pfister, Roman
AU - Michels, Guido
PY - 2018/5
Y1 - 2018/5
N2 - PURPOSE: Patients treated with direct oral anticoagulants (DOACs) frequently undergo interventional procedures requiring temporary discontinuation of anticoagulant therapy. Little is known about remaining peri-procedural exposure to rivaroxaban in real-world patients.METHODS: Fifty-six patients with rivaroxaban treatment and scheduled cardiac catheterization were included in this prospective, observational, and single-center study. Rivaroxaban concentrations were determined by LC-MS/MS and a chromogenic anti-Xa assay. Population pharmacokinetic modeling was carried out on LC-MS/MS concentration data using NONMEM software, and results were applied to Monte Carlo simulations to predict appropriate rivaroxaban discontinuation intervals.RESULTS: Rivaroxaban concentrations ranged from <LLOQ to 300.6 ng/ml at the time of admission to hospital and from <LLOQ to 55.5 ng/ml at the beginning of the procedure. Times since last rivaroxaban intake were (mean ± SD) 51.0 ± 31.7 h (admission) and 85.5 ± 36.8 h (start catheterization). LC-MS/MS and anti-Xa assay results were in good agreement (r = 0.958); however, the anti-Xa assay may underestimate low rivaroxaban concentrations and overestimate rivaroxaban exposure when performed on plasma samples contaminated with heparins. Pharmacokinetics of rivaroxaban were adequately described, and simulations predicted that 95% of patients will have rivaroxaban concentrations ≤ 28.4 ng/ml (15 mg dose group) and ≤ 31.9 ng/ml (20 mg dose group) after 48 h of discontinuation.CONCLUSIONS: In the majority of patients, rivaroxaban plasma concentrations dropped below 30 ng/ml after 48 h of treatment discontinuation which is considered hemostatically safe before surgery with high bleeding risk. For accurate determination of low rivaroxaban concentrations, LC-MS/MS is the preferred choice.
AB - PURPOSE: Patients treated with direct oral anticoagulants (DOACs) frequently undergo interventional procedures requiring temporary discontinuation of anticoagulant therapy. Little is known about remaining peri-procedural exposure to rivaroxaban in real-world patients.METHODS: Fifty-six patients with rivaroxaban treatment and scheduled cardiac catheterization were included in this prospective, observational, and single-center study. Rivaroxaban concentrations were determined by LC-MS/MS and a chromogenic anti-Xa assay. Population pharmacokinetic modeling was carried out on LC-MS/MS concentration data using NONMEM software, and results were applied to Monte Carlo simulations to predict appropriate rivaroxaban discontinuation intervals.RESULTS: Rivaroxaban concentrations ranged from <LLOQ to 300.6 ng/ml at the time of admission to hospital and from <LLOQ to 55.5 ng/ml at the beginning of the procedure. Times since last rivaroxaban intake were (mean ± SD) 51.0 ± 31.7 h (admission) and 85.5 ± 36.8 h (start catheterization). LC-MS/MS and anti-Xa assay results were in good agreement (r = 0.958); however, the anti-Xa assay may underestimate low rivaroxaban concentrations and overestimate rivaroxaban exposure when performed on plasma samples contaminated with heparins. Pharmacokinetics of rivaroxaban were adequately described, and simulations predicted that 95% of patients will have rivaroxaban concentrations ≤ 28.4 ng/ml (15 mg dose group) and ≤ 31.9 ng/ml (20 mg dose group) after 48 h of discontinuation.CONCLUSIONS: In the majority of patients, rivaroxaban plasma concentrations dropped below 30 ng/ml after 48 h of treatment discontinuation which is considered hemostatically safe before surgery with high bleeding risk. For accurate determination of low rivaroxaban concentrations, LC-MS/MS is the preferred choice.
KW - Journal Article
U2 - 10.1007/s00228-018-2421-9
DO - 10.1007/s00228-018-2421-9
M3 - SCORING: Journal article
C2 - 29376194
VL - 74
SP - 611
EP - 618
JO - EUR J CLIN PHARMACOL
JF - EUR J CLIN PHARMACOL
SN - 0031-6970
IS - 5
ER -