Heparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin – a model-based study

Heparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin – a model-based study

Thomas Edrich,1,2 Gyorgy Frendl,2 Gregory Michaud,3 Ioannis Ch Paschalidis4 1Department of Anesthesiology, Perioperative Medicine and General Intensive Care Medicine, Salzburg General Hospital and Paracelsus Private Medical University, Salzburg, Austria, 2Department of Anesthesiology, Perioperative...

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Autores principales: Edrich T, Frendl G, Michaud G, Paschalidis I Ch
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
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Therapeutics. Pharmacology
RM1-950
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spelling oai:doaj.org-article:692e1aff5ffe4288964c1c0ea614792c2021-12-02T05:55:37ZHeparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin – a model-based study1179-1438https://doaj.org/article/692e1aff5ffe4288964c1c0ea614792c2015-02-01T00:00:00Zhttp://www.dovepress.com/heparin-requirements-for-full-anticoagulation-are-higher-for-patients--peer-reviewed-article-CPAAhttps://doaj.org/toc/1179-1438 Thomas Edrich,1,2 Gyorgy Frendl,2 Gregory Michaud,3 Ioannis Ch Paschalidis4 1Department of Anesthesiology, Perioperative Medicine and General Intensive Care Medicine, Salzburg General Hospital and Paracelsus Private Medical University, Salzburg, Austria, 2Department of Anesthesiology, Perioperative and Pain Medicine, 3Department of Medicine, Division of Cardiology, Brigham and Women's Hospital, Harvard Medical School, 4Department of Electrical and Computer Engineering, Division of Systems Engineering, Boston University, Boston, MA, USA Purpose: Dabigatran (D) is increasingly used for chronic anticoagulation in place of warfarin (W). These patients may present for catheter-based procedures requiring full anticoagulation with heparin. This study compares the heparin sensitivity of patients previously on dabigatran, on warfarin, or on no chronic anticoagulant during ablation of atrial fibrillation. Patients and methods: In a retrospective study of patients treated with D, W, or neither drug (N) undergoing atrial ablation, the timing of heparin doses and resulting activated clotting times were collected. First, the initial activated clotting time response to the first heparin bolus was compared. Then, a non-linear mixed effects modelling (NONMEM) analysis was performed, fitting a pharmacokinetic and -dynamic model to the entire anticoagulation course of each patient. Resulting model coefficients were used to compare the different patient groups. Results: Data for 66 patients on dabigatran, 95 patients on warfarin, and 27 patients on no anticoagulation were retrieved. The last dose of dabigatran or warfarin had occurred 27 hours and 15 hours before the procedure. Groups D and N both responded significantly less (P<0.05) to the initial heparin bolus than Group W (approximately 50%). Likewise, the model coefficients resulting from the fit to each group reflected a significantly lower heparin sensitivity in groups D and N compared to W. Clearances of the heparin effect in the model did not differ significantly among groups. Conclusion: Patients on warfarin with an average INR of 1.5 or higher are more sensitive to heparin than patients not previously anticoagulated or patients who discontinued dabigatran 27 hours earlier (approximately two half-lives) warfarin. Keywords: atrial fibrillation, electrophysiology, NONMEM, PKPD modelEdrich TFrendl GMichaud GPaschalidis I ChDove Medical PressarticleTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol 2015, Iss default, Pp 19-27 (2015)
institution DOAJ
collection DOAJ
language EN
topic Therapeutics. Pharmacology
RM1-950
spellingShingle Therapeutics. Pharmacology
RM1-950
Edrich T
Frendl G
Michaud G
Paschalidis I Ch
Heparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin – a model-based study
description Thomas Edrich,1,2 Gyorgy Frendl,2 Gregory Michaud,3 Ioannis Ch Paschalidis4 1Department of Anesthesiology, Perioperative Medicine and General Intensive Care Medicine, Salzburg General Hospital and Paracelsus Private Medical University, Salzburg, Austria, 2Department of Anesthesiology, Perioperative and Pain Medicine, 3Department of Medicine, Division of Cardiology, Brigham and Women's Hospital, Harvard Medical School, 4Department of Electrical and Computer Engineering, Division of Systems Engineering, Boston University, Boston, MA, USA Purpose: Dabigatran (D) is increasingly used for chronic anticoagulation in place of warfarin (W). These patients may present for catheter-based procedures requiring full anticoagulation with heparin. This study compares the heparin sensitivity of patients previously on dabigatran, on warfarin, or on no chronic anticoagulant during ablation of atrial fibrillation. Patients and methods: In a retrospective study of patients treated with D, W, or neither drug (N) undergoing atrial ablation, the timing of heparin doses and resulting activated clotting times were collected. First, the initial activated clotting time response to the first heparin bolus was compared. Then, a non-linear mixed effects modelling (NONMEM) analysis was performed, fitting a pharmacokinetic and -dynamic model to the entire anticoagulation course of each patient. Resulting model coefficients were used to compare the different patient groups. Results: Data for 66 patients on dabigatran, 95 patients on warfarin, and 27 patients on no anticoagulation were retrieved. The last dose of dabigatran or warfarin had occurred 27 hours and 15 hours before the procedure. Groups D and N both responded significantly less (P<0.05) to the initial heparin bolus than Group W (approximately 50%). Likewise, the model coefficients resulting from the fit to each group reflected a significantly lower heparin sensitivity in groups D and N compared to W. Clearances of the heparin effect in the model did not differ significantly among groups. Conclusion: Patients on warfarin with an average INR of 1.5 or higher are more sensitive to heparin than patients not previously anticoagulated or patients who discontinued dabigatran 27 hours earlier (approximately two half-lives) warfarin. Keywords: atrial fibrillation, electrophysiology, NONMEM, PKPD model
format article
author Edrich T
Frendl G
Michaud G
Paschalidis I Ch
author_facet Edrich T
Frendl G
Michaud G
Paschalidis I Ch
author_sort Edrich T
title Heparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin – a model-based study
title_short Heparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin – a model-based study
title_full Heparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin – a model-based study
title_fullStr Heparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin – a model-based study
title_full_unstemmed Heparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin – a model-based study
title_sort heparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin – a model-based study
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/692e1aff5ffe4288964c1c0ea614792c
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AT michaudg heparinrequirementsforfullanticoagulationarehigherforpatientsondabigatranthanforthoseonwarfarinndashamodelbasedstudy
AT paschalidisich heparinrequirementsforfullanticoagulationarehigherforpatientsondabigatranthanforthoseonwarfarinndashamodelbasedstudy
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