title: An anti-von Willebrand factor aptamer reduces platelet adhesion among patients receiving aspirin and clopidogrel in an ex vivo shear-induced arterial thrombosis.
abstract: The von Willebrand factor (vWF) aptamer, ARC1779 that blocks the binding of vWF A1-domain to platelet glycoprotein 1b (GPIb) at high shear, may deliver a site-specific antithrombotic effect. We investigated the efficiency of ARC1779 on platelet function in patients with coronary artery disease (CAD) on double antiplatelet therapy. Blood from patients taking aspirin and clopidogrel and from normal volunteers was treated ex vivo with ARC1779 or abciximab, either prior to perfusion (pretherapy) or 10 minutes following the initiation of perfusion (posttherapy) on damaged arteries. Under pre- but not posttherapy, platelet adhesion was significantly reduced by ARC1779 at 83 and 250 nmol/L and by abciximab (100 nmol/L) versus placebo (4.8, 3.8, and 2.9 vs 7.3 platelets × 10(6)/cm(2), P < .05). In contrast to abciximab, ARC1779 did not significantly affect platelet aggregation, P-selectin expression, and platelet-leukocyte binding. These proof-of-concept data may constitute the framework for randomized clinical investigations of this novel antiplatelet therapy among patients with CAD.
authors.affiliation: Department of Medicine, Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors.forename: Dabit
authors.initials: D
authors.lastname: Arzamendi
authors.forename: Firas
authors.initials: F
authors.lastname: Dandachli
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Théorêt
authors.forename: Gregory
authors.initials: G
authors.lastname: Ducrocq
authors.forename: Mark
authors.initials: M
authors.lastname: Chan
authors.forename: Walid
authors.initials: W
authors.lastname: Mourad
authors.forename: James C
authors.initials: JC
authors.lastname: Gilbert
authors.forename: Robert G
authors.initials: RG
authors.lastname: Schaub
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Tanguay
authors.forename: Yahye
authors.initials: Y
authors.lastname: Merhi
mesh_terms: D000077284:Abciximab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D052157:Aptamers, Nucleotide / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014841:von Willebrand Factor / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C526287:ARC 1779; D000911:Antibodies, Monoclonal; D052157:Aptamers, Nucleotide; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D014841:von Willebrand Factor; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin; D000077284:Abciximab