title: Effect of aspirin, clopidogrel and dipyridamole on soluble markers of vascular function in normal volunteers and patients with prior ischaemic stroke.
abstract: Although the mechanisms of action by which aspirin, clopidogrel and dipyridamole inhibit platelets are well characterised, their effects on soluble modulators of thrombosis, inflammation, and endothelial function have yet to assessed systematically. In this investigation aspirin (A), clopidogrel (C), and dipyridamole (D) were administered singly and in combination (A, C, D, AC, AD, CD, ACD) in random order for 2 weeks (without washout) to 11 healthy subjects and 11 patients with previous ischaemic stroke. At the end of each treatment period plasma cyclic guanosine monophosphate (cGMP), monocyte chemoattractant pertide-1 (MCP-1), nitric oxide metabolites (NO(x)), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWf); and serum C-reactive protein (CRP) and platelet derived growth factor (PDGF); were measured blinded to treatment. Dipyridamole reduced plasma vWf levels (%) in both volunteers, -10.0 (4.95), and patients, -10.11 (4.34) (p < 0.05). Dipyridamole also lowered CRP (mg/l) in patients, -0.96 (0.47), but not volunteers. Clopidogrel reduced PAI-1 (ng/ml) in volunteers, -5.30 (2.20) (p < 0.05), and patients, -3.61 (2.75) (non-significant trend). Aspirin lowered PDGF (ng/ml) in volunteers, -3.46 (1.55), but not patients. Triple antiplatelet therapy was superior to dual and mono therapy in reducing vWf levels. In conclusion, antiplatelet agents have non-platelet-related effects on soluble modulators of thrombosis, inflammation, and endothelial function. In particular, dipyridamole reduces plasma vWf and clopidogrel lowers plasma PAI-1 levels. These effects may explain, in part, their roles in preventing atherothrombogenesis.
authors.affiliation: Clinical Research, University of Nottingham, Nottingham, UK.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhao
authors.forename: Laura
authors.initials: L
authors.lastname: Gray
authors.forename: Jo
authors.initials: J
authors.lastname: Leonardi-Bee
authors.forename: Chris S
authors.initials: CS
authors.lastname: Weaver
authors.forename: Stan
authors.initials: S
authors.lastname: Heptinstall
authors.forename: Philip M W
authors.initials: PM
authors.lastname: Bath
mesh_terms: D000328:Adult; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy; D001241:Aspirin / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000175:diagnosis / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000187:drug effects; D000077144:Clopidogrel; D003430:Cross-Sectional Studies; D004176:Dipyridamole / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000378:metabolism; D010976:Platelet Count; D010982:Platelet-Derived Growth Factor / Q000187:drug effects; D012995:Solubility; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000187:drug effects
chemical_list: D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D010982:Platelet-Derived Growth Factor; D014841:von Willebrand Factor; D004176:Dipyridamole; D002097:C-Reactive Protein; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin