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European Journal of Clinical Pharmacology

, Volume 74, Issue 5, pp 611–618 | Cite as

Residual rivaroxaban exposure after discontinuation of anticoagulant therapy in patients undergoing cardiac catheterization

  • Martin H. J. Wiesen
  • Cornelia Blaich
  • Max Taubert
  • Veronika Jennissen
  • Thomas Streichert
  • Roman Pfister
  • Guido Michels
Pharmacokinetics and Disposition

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.

Keywords

Oral anticoagulation Rivaroxaban Discontinuation Cardiac catheterization Mass spectrometry Anti-Xa assay 

Notes

Acknowledgements

The authors thank the medical and nursing staff of the Department of Cardiology for kind and invaluable support.

Compliance with ethical standards

This study was approved by the local Ethics Committee of the University Hospital of Cologne (14-066) and carried out in accordance with the Helsinki declaration (DRKS00006002).

Conflict of interest

Dr. Wiesen reports personal fees from Pfizer Pharma GmbH, outside the submitted work. All other authors report no conflicts of interest.

Supplementary material

228_2018_2421_MOESM1_ESM.pdf (877 kb)
ESM 1 (PDF 876 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Center of Pharmacology, Therapeutic Drug Monitoring UnitUniversity Hospital of CologneCologneGermany
  2. 2.Center of Pharmacology, Department I of Pharmacology, Clinical Pharmacology UnitUniversity Hospital of CologneCologneGermany
  3. 3.Institute for Clinical ChemistryUniversity Hospital of CologneCologneGermany
  4. 4.Department III of Internal Medicine, Cardiology, Heart CenterUniversity Hospital of CologneCologneGermany

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