Universität zu Köln

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

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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
Creators:	Creators Email ORCID ORCID Put Code Wiesen, Martin H. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Blaich, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Taubert, Max UNSPECIFIED orcid.org/0000-0001-8925-7782 UNSPECIFIED Jennissen, Veronika UNSPECIFIED UNSPECIFIED UNSPECIFIED Streichert, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfister, Roman UNSPECIFIED UNSPECIFIED UNSPECIFIED Michels, Guido UNSPECIFIED UNSPECIFIED UNSPECIFIED
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
Uncontrolled Keywords:	Keywords Language DIRECT ORAL ANTICOAGULANTS; NONVALVULAR ATRIAL-FIBRILLATION; HUMAN PLASMA; MANAGEMENT; DABIGATRAN; SURGERY; QUANTIFICATION; COMPLICATIONS; INTERVENTION; ASSOCIATION Multiple languages Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18689