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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.
MedLine Citation:
PMID:  21925716     Owner:  NLM     Status:  Publisher    
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.
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:
Type:  JOURNAL ARTICLE     Date:  2011-9-16
Journal Detail:
Title:  Thrombosis research     Volume:  -     ISSN:  1879-2472     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0326377     Medline TA:  Thromb Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Department of Clinical Pharmacology, Medical University of Vienna, Austria.
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