Tinzaparin, an alternative to subcutaneous unfractionated heparin, in patients with severe and end-stage renal impairment: a retrospective observational single-center study.

Autor:	Gouin-Thibault I; Department of Laboratory Hematology, Pontchaillou University Hospital of Rennes, Rennes, France; Institut de Recherche en Santé, Environnement et Travail (IRSET)-Institut National de la Santé et de la Recherche Médicale (INSERM)-1085, University of Rennes, Rennes, France. Electronic address: Isabelle.gouin@chu-rennes.fr., Mansour A; Institut de Recherche en Santé, Environnement et Travail (IRSET)-Institut National de la Santé et de la Recherche Médicale (INSERM)-1085, University of Rennes, Rennes, France; Department of Anesthesia and Critical Care, Pontchaillou University Hospital of Rennes, Rennes, France., Caribotti C; Department of Pharmacy, Pontchaillou University Hospital of Rennes, Rennes, France., Pierre-Jean M; Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI) -1099, University of Rennes, Pontchaillou University Hospital of Rennes, Rennes, France., Bouzille G; Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI) -1099, University of Rennes, Pontchaillou University Hospital of Rennes, Rennes, France., Ballerie A; Department of Internal Medicine and Clinical Immunology, Rennes University Hospital, Rennes, France., Maucorps L; Department of Laboratory Hematology, Pontchaillou University Hospital of Rennes, Rennes, France., Gueret P; Department of Laboratory Hematology, Pontchaillou University Hospital of Rennes, Rennes, France., Nédelec-Gac F; Department of Laboratory Hematology, Pontchaillou University Hospital of Rennes, Rennes, France., Pontis A; Department of Laboratory Hematology, Pontchaillou University Hospital of Rennes, Rennes, France; Institut de Recherche en Santé, Environnement et Travail (IRSET)-Institut National de la Santé et de la Recherche Médicale (INSERM)-1085, University of Rennes, Rennes, France., Mahé G; Vascular Medicine Department, Radiology and Medical Imaging Department, Rennes University Hospital Centre, Rennes, France., Vannier S; Department of Neurology, Rennes University Hospital, Rennes, France., Behar N; Department of Cardiology, Rennes University Hospital, Rennes, France., Cardiet I; Department of Pharmacy, Pontchaillou University Hospital of Rennes, Rennes, France., Mismetti P; Therapeutic and Vascular Medicine Department, Saint-Étienne University Hospital, Saint-Etienne, France; Institut National de la Santé et de la Recherche Médicale (INSERM)-1059 SAnté INgéniérie BIOlogie St-Etienne (SAINBIOSE), Jean Monnet University, Mines Saint-Étienne, France., Frouget T; Department of Nephrology, Pontchaillou University Hospital of Rennes, Rennes, France., Delavenne X; Institut National de la Santé et de la Recherche Médicale (INSERM)-1059 SAnté INgéniérie BIOlogie St-Etienne (SAINBIOSE), Jean Monnet University, Mines Saint-Étienne, France; Department of Pharmacology, Saint-Étienne University Hospital, Saint-Etienne, France.
Jazyk:	angličtina
Zdroj:	Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2024 Oct; Vol. 22 (10), pp. 2864-2872. Date of Electronic Publication: 2024 Jul 15.
DOI:	10.1016/j.jtha.2024.07.006
Abstrakt:	Background: Tinzaparin could be easier to manage than unfractionated heparin in patients with severe renal impairment. However, clinical and pharmacologic data regarding its use in such patients are lacking. Objectives: The aims of this study were to determine, in patients with estimated glomerular filtration rate (eGFR) of <30 mL.min⁻ 1 , tinzaparin pharmacokinetics (PK) parameters using a population PK approach and bleeding and thrombotic complications. Methods: We performed a retrospective observational single-center study, including in-patients with eGFR of <30 mL.min⁻ 1 receiving prophylactic (4500 IU.d⁻ 1 ) or therapeutic (175 IU.kg⁻ 1 .d⁻ 1 ) tinzaparin. Measured anti-Xa levels were analyzed using a nonlinear mixed-effects modeling approach. Individual predicted tinzaparin exposure markers at steady state were calculated for each patient and dosing regimen. The PK was also evaluated through Monte Carlo simulations based on the final covariate model parameter estimates. Results: Over a 22-month period, 802 tinzaparin treatment periods in 623 patients were analyzed: two-thirds received a prophylactic dose, 66% had an eGFR of <20 mL.min⁻ 1 , and 25% were on renal replacement therapy. In patients for whom anti-Xa measurements were performed (n = 199; 746 values), PK parameters, profiles, and maximum plasma concentrations were comparable with those in patients without renal impairment or in healthy volunteers. In the whole population, major bleeding occurred in 2.4% and 3.5% of patients receiving prophylactic and therapeutic doses over a median 9- and 7-day treatment period, respectively. No patients had thrombotic complications. Conclusion: Tinzaparin PK parameters and profiles were not affected by renal impairment. This suggests that tinzaparin, at therapeutic or prophylactic dose, could be an alternative to unfractionated heparin in hospitalized patients with severe renal impairment. Competing Interests: Declaration of competing interests I.G.T. has received honoraria from Aguettant, Bayer, BMS-Pfizer, Leo-Pharma, Sanofi, Stago, and Viatris. G.M. has received honoraria from Bayer Healthcare, BMS-Pfizer, Leo-Pharma, and Sanofi. P.M. has received honoraria from Bayer Healthcare, BMS-Pfizer, Leo-Pharma, and Sanofi. P.G. has received honoraria from Sanofi. All other authors declare no conflicts of interest. (Copyright © 2024. Published by Elsevier Inc.)
Databáze:	MEDLINE
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