title: Clopidogrel improves microvascular endothelial function in subjects with stable coronary artery disease.
abstract: BACKGROUND
  Clopidogrel therapy has recently been shown to reduce cardiovascular events in patients with stable vascular disease. This benefit may be due to effects not exclusively related to platelet aggregation. The aim of this study was to evaluate the effect of clopidogrel therapy on microvascular endothelial function in subjects with stable coronary artery disease (CAD).
  
  
  RESULTS
  Forty subjects with stable CAD were randomised to clopidogrel therapy (75mg/day) or control. Blood and endothelial function testing occurred at baseline, one week and three months following randomisation. Microvascular endothelial function was assessed via reactive hyperaemic index (RHI). Platelet function was assessed by adenosine diphosphate (ADP)-induced whole blood aggregation and the VerifyNow™ system. Plasma markers of endothelial function (asymmetric dimethylarginine, ADMA) and oxidative stress (myeloperoxidase, MPO) were also tested. The primary endpoint was endothelial function assessment (RHI) at three months. At one week RHI increased by 20±10% in the clopidogrel group; this effect was maintained at three months (21±9% increase from baseline; P<0.01). A significant decrease in ADP-induced platelet aggregation and P2Y12 reaction units was observed in the clopidogrel therapy group (P<0.01). There was no correlation between endothelial function and platelet function testing in the clopidogrel therapy group.
  
  
  CONCLUSIONS
  Clopidogrel therapy is associated with improved microvascular endothelial function in patients with stable CAD. This effect is independent of its effects on ADP-induced platelet reactivity.
authors: Centre for Heart Rhythm Disorders, University of Adelaide, Adelaide, Australia.
authors: Scott R
authors: SR
authors: Willoughby
authors: Monash Cardiovascular Research Centre, MonashHeart and Monash University, Melbourne, Australia; Cardiovascular Research Centre, Royal Adelaide Hospital, University of Adelaide, Australia.
authors: Lee-Jen
authors: LJ
authors: Luu
authors: Monash Cardiovascular Research Centre, MonashHeart and Monash University, Melbourne, Australia.
authors: James D
authors: JD
authors: Cameron
authors: Cardiovascular Research Centre, Royal Adelaide Hospital, University of Adelaide, Australia.
authors: Adam J
authors: AJ
authors: Nelson
authors: Centre for Heart Rhythm Disorders, University of Adelaide, Adelaide, Australia.
authors: Carlee D
authors: CD
authors: Schultz
authors: Cardiovascular Research Centre, Royal Adelaide Hospital, University of Adelaide, Australia.
authors: Stephen G
authors: SG
authors: Worthley
authors: Cardiovascular Research Centre, Royal Adelaide Hospital, University of Adelaide, Australia. Electronic address: matthew.worthley@adelaide.edu.au.
authors: Matthew I
authors: MI
authors: Worthley
mesh_terms: D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D055806:Microvessels / Q000378:metabolism*; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: Clopidogrel; Coronary artery disease; Endothelial function; Nitric oxide; Platelet aggregation