| Effect on perfusion chamber thrombus size in patients with atrial fibrillation during anticoagulant treatment with oral direct thrombin inhibitors, AZD0837 or ximelagatran, or with vitamin K antagonists. | |
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MedLine Citation:
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PMID: 21925716 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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INTRODUCTION: AZD0837 and ximelagatran are oral direct thrombin inhibitors that are rapidly absorbed and bioconverted to their active forms, AR-H067637 and melagatran, respectively. This study investigated the antithrombotic effect of AZD0837, compared to ximelagatran and the vitamin K antagonist (VKA) phenprocoumon (Marcoumar(®)), in a disease model of thrombosis in patients with non-valvular atrial fibrillation (NVAF). METHODS: Open, parallel-group studies were performed in NVAF patients treated with VKA, which was stopped aiming for an international normalized ratio (INR) of ≤2 before randomization. Study I: 38 patients randomized to AZD0837 (150,250 or 350mg) or ximelagatran 36mg twice daily for 10-14days. Study II: 27 patients randomized to AZD0837 250mg twice daily or VKA titrated to an INR of 2-3 for 10-14days. A control group of 20 healthy elderly subjects without NVAF or anticoagulant treatment was also studied. Size of thrombus formed on pig aorta strips was measured after a 5-minute perfusion at low shear rate with blood from the patient/control subject. RESULTS: Thrombus formation was inhibited by AZD0837 and ximelagatran. Relative to untreated patients, a 50% reduction of thrombus size was estimated at plasma concentrations of 0.6 and 0.2μmol/L for AR-H067637 and melagatran, respectively. For patients receiving VKA treatment, the thrombus size was about 15% lower compared with healthy elderly controls. CONCLUSIONS: Effects of AZD0837 and ximelagatran on thrombus formation were similar or greater than for VKA therapy and correlated with plasma concentrations of their active forms. |
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Authors:
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Michael Wolzt; Ulf G Eriksson; Ghazaleh Gouya; Nicolai Leuchten; Stylianos Kapiotis; Margareta Elg; Kajs-Marie Schützer; Sofia Zetterstrand; Malin Holmberg; Karin Wåhlander |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-16 |
Journal Detail:
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Title: Thrombosis research Volume: - ISSN: 1879-2472 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0326377 Medline TA: Thromb Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Clinical Pharmacology, Medical University of Vienna, Austria. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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