Alexander Kaserer1, Andreas Schedler1, Alexander Jetter2, Burkhardt Seifert3, Donat R Spahn1, Philipp Stein1, Jan-Dirk Studt4. 1. Institute of Anaesthesiology, University and University Hospital Zurich, Zurich, Switzerland. 2. Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland. 3. Department of Biostatistics and Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland. 4. Division of Haematology, University and University Hospital Zurich, Zurich, Switzerland.
Abstract
INTRODUCTION: Rivaroxaban (RXA) is a direct oral factor Xa (Xa) antagonist with a short half-life and a fast onset and offset of effect. Before elective surgery, discontinuation is recommended with an interval of at least > 24 hours. In clinical practice, this is, however, not always sufficient to achieve a residual RXA plasma concentration deemed appropriate for surgery, defined as ≤ 50 mcg/L. Our study aimed at identifying factors associated with a higher-than-expected residual RXA plasma concentration in a large group of real-life patients. MATERIALS AND METHODS: This retrospective single-centre study included all patients taking RXA between 2012 and 2016 where RXA plasma concentration was determined by pharmacodynamic anti-Xa assay (518 measurements in 368 patients). Medical records were reviewed. Residual RXA plasma concentrations were then compared with expected values according to a pharmacokinetic model. RESULTS: Residual RXA plasma concentration was significantly higher-than-expected in patients with atrial fibrillation, impaired kidney function (glomerular filtration rate [GFR] < 60 mL/min), CYP3A4-, CYP2J2- and PGP-inhibitory co-medication including amiodarone. Impaired kidney function (odds ratio [OR], 2.22, 95% confidence interval [CI], 1.30-3.78, p = 0.003) and concomitant amiodarone intake (OR, 1.97, 95% CI, 1.04-3.72, p = 0.036) were significantly associated with RXA plasma concentrations > 50 mcg/L at 24 to 48 hours after the last RXA intake. CONCLUSION: In our group of real-life patients, impaired kidney function (GFR < 60 mL/min) and co-medication with amiodarone were independently associated with higher-than-expected residual RXA plasma concentrations. In these patients, standard intervals of RXA discontinuation may not always be sufficient before elective surgery and routine pre-operative determination of the residual RXA concentration could be advisable. Schattauer GmbH Stuttgart.
INTRODUCTION:Rivaroxaban (RXA) is a direct oral factor Xa (Xa) antagonist with a short half-life and a fast onset and offset of effect. Before elective surgery, discontinuation is recommended with an interval of at least > 24 hours. In clinical practice, this is, however, not always sufficient to achieve a residual RXA plasma concentration deemed appropriate for surgery, defined as ≤ 50 mcg/L. Our study aimed at identifying factors associated with a higher-than-expected residual RXA plasma concentration in a large group of real-life patients. MATERIALS AND METHODS: This retrospective single-centre study included all patients taking RXA between 2012 and 2016 where RXA plasma concentration was determined by pharmacodynamic anti-Xa assay (518 measurements in 368 patients). Medical records were reviewed. Residual RXA plasma concentrations were then compared with expected values according to a pharmacokinetic model. RESULTS: Residual RXA plasma concentration was significantly higher-than-expected in patients with atrial fibrillation, impaired kidney function (glomerular filtration rate [GFR] < 60 mL/min), CYP3A4-, CYP2J2- and PGP-inhibitory co-medication including amiodarone. Impaired kidney function (odds ratio [OR], 2.22, 95% confidence interval [CI], 1.30-3.78, p = 0.003) and concomitant amiodarone intake (OR, 1.97, 95% CI, 1.04-3.72, p = 0.036) were significantly associated with RXA plasma concentrations > 50 mcg/L at 24 to 48 hours after the last RXA intake. CONCLUSION: In our group of real-life patients, impaired kidney function (GFR < 60 mL/min) and co-medication with amiodarone were independently associated with higher-than-expected residual RXA plasma concentrations. In these patients, standard intervals of RXA discontinuation may not always be sufficient before elective surgery and routine pre-operative determination of the residual RXA concentration could be advisable. Schattauer GmbH Stuttgart.
Authors: Tamana Meihandoest; Jan-Dirk Studt; Adriana Mendez; Lorenzo Alberio; Pierre Fontana; Walter A Wuillemin; Adrian Schmidt; Lukas Graf; Bernhard Gerber; Ursula Amstutz; Cedric Bovet; Thomas C Sauter; Lars M Asmis; Michael Nagler Journal: Front Cardiovasc Med Date: 2022-03-17
Authors: Vepusha Sathanantham; Lorenzo Alberio; Cédric Bovet; Pierre Fontana; Bernhard Gerber; Lukas Graf; Adriana Mendez; Thomas C Sauter; Adrian Schmidt; Jan-Dirk Studt; Walter A Wuillemin; Michael Nagler Journal: Life (Basel) Date: 2022-07-11
Authors: Anne-Laure Sennesael; Anne-Sophie Larock; Jonathan Douxfils; Laure Elens; Gabriel Stillemans; Martin Wiesen; Max Taubert; Jean-Michel Dogné; Anne Spinewine; François Mullier Journal: Thromb J Date: 2018-11-12
Authors: Alexander Kaserer; Andreas Schedler; Burkhardt Seifert; Donat R Spahn; Jan-Dirk Studt; Philipp Stein Journal: Perioper Med (Lond) Date: 2019-11-20