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Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: A Phase II study of AZD0837 in patients who are appropriate for but unable or unwilling to take vitamin K antagonist therapy

Lip, Gregory Y. H. ; Rasmussen, Lars H. ; Olsson, Bertil LU ; Zetterstrand, Sofia ; Stahre, Christina ; Bylock, Anders ; Aunes-Jansson, Maria ; Eriksson, Ulf and Wahlander, Karin (2011) In Thrombosis Research 127(2). p.91-99
Abstract
Background: Some patients with atrial fibrillation (AF) cannot be treated with vitamin K antagonists (VKAs) and will therefore not receive effective thromboprophylaxis. The primary objective of the present Phase II trial (NCT00623779) was to assess the feasibility of conducting a study with a novel oral anticoagulant, the direct thrombin inhibitor AZD0837, in patients with AF unable or unwilling to take warfarin, by evaluation of dropout rates and compliance. Methods: Patients were randomised to receive AZD0837 extended-release tablets 150 mg (n = 43) or 300 mg (n = 42) once daily, or standard therapy (no treatment, aspirin 75-325 mg or clopidogrel 75 mg once daily; n = 46) for a median treatment duration of 6 weeks. Results: Reasons for... (More)
Background: Some patients with atrial fibrillation (AF) cannot be treated with vitamin K antagonists (VKAs) and will therefore not receive effective thromboprophylaxis. The primary objective of the present Phase II trial (NCT00623779) was to assess the feasibility of conducting a study with a novel oral anticoagulant, the direct thrombin inhibitor AZD0837, in patients with AF unable or unwilling to take warfarin, by evaluation of dropout rates and compliance. Methods: Patients were randomised to receive AZD0837 extended-release tablets 150 mg (n = 43) or 300 mg (n = 42) once daily, or standard therapy (no treatment, aspirin 75-325 mg or clopidogrel 75 mg once daily; n = 46) for a median treatment duration of 6 weeks. Results: Reasons for patients not being treated with warfarin were: refusal or permanent cessation decided by the patient (64.8%), inability to keep international normalised ratio 2-3 over a 3-month period (23.2%), physician assessment that VKA was inappropriate (20.4%) and warfarin allergy (2.8%). Compliance with treatment (mean +/- SD) was 97.0 +/- 16.5% for AZD0837 150 mg and 99.8 +/- 11.4% for 300 mg. Compliance with study visits was high (mean 93-98%). The numbers of dropouts were four, six and three, whilst minor or clinically significant minor bleeds were reported in zero, five and two patients in the AZD0837 150 mg, 300 mg and standard-therapy groups, respectively. No major bleeds were reported. Both doses of AZD0837 reduced levels of fibrin D-dimer and prolonged activated partial thromboplastin time, ecarin clotting time and thrombin clotting time. Conclusions: AZD0837 had a good safety profile during this study, including a low incidence of bleeding events, with effective anticoagulation on pharmacodynamic parameters. A larger study in AF patients unable or unwilling to take warfarin is feasible, as judged by compliance and dropout rates. (C) 2010 Elsevier Ltd. All rights reserved. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
AZD0837, Atrial fibrillation, Anticoagulation, Vitamin K antagonist, Oral direct thrombin inhibitor
in
Thrombosis Research
volume
127
issue
2
pages
91 - 99
publisher
Elsevier
external identifiers
  • wos:000286453800006
  • scopus:79151471916
  • pmid:21172721
ISSN
1879-2472
DOI
10.1016/j.thromres.2010.11.012
language
English
LU publication?
yes
id
fc7a426c-10dd-4305-b850-ed5182ceaaef (old id 1790661)
date added to LUP
2016-04-01 10:53:24
date last changed
2025-04-04 14:56:00
@article{fc7a426c-10dd-4305-b850-ed5182ceaaef,
  abstract     = {{Background: Some patients with atrial fibrillation (AF) cannot be treated with vitamin K antagonists (VKAs) and will therefore not receive effective thromboprophylaxis. The primary objective of the present Phase II trial (NCT00623779) was to assess the feasibility of conducting a study with a novel oral anticoagulant, the direct thrombin inhibitor AZD0837, in patients with AF unable or unwilling to take warfarin, by evaluation of dropout rates and compliance. Methods: Patients were randomised to receive AZD0837 extended-release tablets 150 mg (n = 43) or 300 mg (n = 42) once daily, or standard therapy (no treatment, aspirin 75-325 mg or clopidogrel 75 mg once daily; n = 46) for a median treatment duration of 6 weeks. Results: Reasons for patients not being treated with warfarin were: refusal or permanent cessation decided by the patient (64.8%), inability to keep international normalised ratio 2-3 over a 3-month period (23.2%), physician assessment that VKA was inappropriate (20.4%) and warfarin allergy (2.8%). Compliance with treatment (mean +/- SD) was 97.0 +/- 16.5% for AZD0837 150 mg and 99.8 +/- 11.4% for 300 mg. Compliance with study visits was high (mean 93-98%). The numbers of dropouts were four, six and three, whilst minor or clinically significant minor bleeds were reported in zero, five and two patients in the AZD0837 150 mg, 300 mg and standard-therapy groups, respectively. No major bleeds were reported. Both doses of AZD0837 reduced levels of fibrin D-dimer and prolonged activated partial thromboplastin time, ecarin clotting time and thrombin clotting time. Conclusions: AZD0837 had a good safety profile during this study, including a low incidence of bleeding events, with effective anticoagulation on pharmacodynamic parameters. A larger study in AF patients unable or unwilling to take warfarin is feasible, as judged by compliance and dropout rates. (C) 2010 Elsevier Ltd. All rights reserved.}},
  author       = {{Lip, Gregory Y. H. and Rasmussen, Lars H. and Olsson, Bertil and Zetterstrand, Sofia and Stahre, Christina and Bylock, Anders and Aunes-Jansson, Maria and Eriksson, Ulf and Wahlander, Karin}},
  issn         = {{1879-2472}},
  keywords     = {{AZD0837; Atrial fibrillation; Anticoagulation; Vitamin K antagonist; Oral direct thrombin inhibitor}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{91--99}},
  publisher    = {{Elsevier}},
  series       = {{Thrombosis Research}},
  title        = {{Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: A Phase II study of AZD0837 in patients who are appropriate for but unable or unwilling to take vitamin K antagonist therapy}},
  url          = {{http://dx.doi.org/10.1016/j.thromres.2010.11.012}},
  doi          = {{10.1016/j.thromres.2010.11.012}},
  volume       = {{127}},
  year         = {{2011}},
}