Wiesen, Martin H. J., Blaich, Cornelia, Taubert, Max ORCID: 0000-0001-8925-7782, Jennissen, Veronika, Streichert, Thomas, Pfister, Roman and Michels, Guido
(2018).
Residual rivaroxaban exposure after discontinuation of anticoagulant therapy in patients undergoing cardiac catheterization.
Eur. J. Clin. Pharmacol., 74 (5).
S. 611 - 619.
HEIDELBERG:
SPRINGER HEIDELBERG.
ISSN 1432-1041
Abstract
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.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-186890 | ||||||||||||||||||||||||||||||||
DOI: | 10.1007/s00228-018-2421-9 | ||||||||||||||||||||||||||||||||
Journal or Publication Title: | Eur. J. Clin. Pharmacol. | ||||||||||||||||||||||||||||||||
Volume: | 74 | ||||||||||||||||||||||||||||||||
Number: | 5 | ||||||||||||||||||||||||||||||||
Page Range: | S. 611 - 619 | ||||||||||||||||||||||||||||||||
Date: | 2018 | ||||||||||||||||||||||||||||||||
Publisher: | SPRINGER HEIDELBERG | ||||||||||||||||||||||||||||||||
Place of Publication: | HEIDELBERG | ||||||||||||||||||||||||||||||||
ISSN: | 1432-1041 | ||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||
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Refereed: | Yes | ||||||||||||||||||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/18689 |
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