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The von Willebrand Inhibitor ARC1779 reduces cerebral embolization after carotid endarterectomy : a randomized trial

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Markus, Hugh S., McCollum, C. (Charles), Imray, C. (Chris), Goulder, M. A., Gilbert, J. (Jim) and King, A. (Alice). (2011) The von Willebrand Inhibitor ARC1779 reduces cerebral embolization after carotid endarterectomy : a randomized trial. Stroke, Vol.42 (No.8). pp. 2149-2153. ISSN 0039-2499

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Abstract

Background and Purpose-Inhibition of von Willebrand factor offers a novel approach to prevention of stroke and myocardial ischemia but has not yet been demonstrated to show efficacy on clinically relevant end points. ARC1779 is an aptamer that inhibits the prothrombotic function of von Willebrand factor by binding to the A1 domain of von Willebrand factor and thereby blocking its interaction with glycoprotein. Phase 1 studies suggest it inhibits platelet aggregation with less increase in bleeding than conventional antiplatelet agents. The effect of ARC 1779 on cerebral emboli immediately after carotid endarterectomy was investigated in a randomized clinical trial.

Methods-Patients undergoing carotid endarterectomy were randomized double-blind to ARC1779 or placebo administered intravenously. Transcranial Doppler recording, to detect cerebral embolic signals, was performed in the first 3 hours postoperatively. The primary end point was time to first embolic signals.

Results-Thirty-six patients were recruited, 18 in each arm. The Kaplan-Meier median time to first embolic signals was 83.6 minutes for ARC1779 compared with 5.5 minutes for placebo. Using Cox proportional hazards embolic signals occurred statistically significantly later on ARC1779 (P=0.007). Reduced embolic signals counts were correlated with inhibition of von Willebrand factor activity (P=0.03). Increased perioperative bleeding and anemia were seen with ARC1779.

Conclusions-von Willebrand factor inhibition reduces thromboembolism in humans. It may play a role in treatment of stroke and myocardial ischemia. The extent to which bleeding complications occur in nonoperated patients needs to be assessed in further studies.

Item Type: Journal Article
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Von Willebrand factor, Blood coagulation factor VIII antibodies, Clinical trials, Cerebrovascular disease -- Prevention, Embolism -- Treatment, Endarterectomy, Transcranial Doppler ultrasonography
Journal or Publication Title: Stroke
Publisher: Lippincott Williams & Wilkins
ISSN: 0039-2499
Official Date: August 2011
Volume: Vol.42
Number: No.8
Page Range: pp. 2149-2153
Identification Number: 10.1161/STROKEAHA.111.616649
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: Archimex Corp.
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URI: http://wrap.warwick.ac.uk/id/eprint/38571

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