title: Effect of clopidogrel withdrawal on platelet reactivity and vascular inflammatory biomarkers 1 year after drug-eluting stent implantation: results of the prospective, single-centre CESSATION study.
abstract: BACKGROUND
  The optimal duration of clopidogrel treatment, particularly following drug-eluting stent (DES) implantation, remains contentious. Previous studies have observed a clustering of adverse events following clopidogrel cessation 1 year after DES, the aetiology of which is poorly understood.
  
  
  OBJECTIVE
  To investigate, in the prospective CESSATION study, the effect of clopidogrel withdrawal at 1 year after DES implantation on (i) arachidonic acid (AA)- and adenosine diphosphate (ADP)-induced platelet aggregation, and (ii) biomarkers of vascular inflammation, including soluble CD40 ligand (sCD40L), high-sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6).
  
  
  RESULTS
  The prospective CESSATION study was undertaken in 33 patients receiving aspirin and due to discontinue clopidogrel 1 year after DES. Platetet reactivity was measured using short thromboelastography, and compliance with aspirin determined from serum thromboxane B(2) (TXB(2)) levels. Venesection was performed at 4 weeks and 24 h before, and at 24 h, 48 h, 1, 2 and 4 weeks after, clopidogrel cessation. Following clopidogrel withdrawal, there was (i) a predictable increase in ADP-induced platelet aggregation (ii) an unexpected significant increase in AA-induced platelet aggregation (iii) a decline in IL-6 and hsCRP at 1 week and 4 weeks respectively; and (iv) a non-significant increase in sCD40L at 4 weeks TXB(2) levels were consistently suppressed, indicating complete inhibition of cyclo-oxygenase-1 by aspirin.
  
  
  CONCLUSIONS
  An aspirin-independent, time-dependent increase in AA-induced platelet activation following clopidogrel withdrawal in patients with a DES has been described. New insights into a potential mechanism for the observed clustering of adverse events that occur early after clopidogrel cessation have been provided. These findings raise the question as to whether AA-induced clotting is an appropriate test of aspirin sensitivity.
authors.affiliation: Wessex Cardiothoracic Unit, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. nick.curzen@suht.swest.nhs.uk
authors.forename: Nalyaka
authors.initials: N
authors.lastname: Sambu
authors.forename: Hazel
authors.initials: H
authors.lastname: Dent
authors.forename: Nicola
authors.initials: N
authors.lastname: Englyst
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Warner
authors.forename: Philip
authors.initials: P
authors.lastname: Leadbeater
authors.forename: Paul
authors.initials: P
authors.lastname: Roderick
authors.forename: Huon
authors.initials: H
authors.lastname: Gray
authors.forename: Iain
authors.initials: I
authors.lastname: Simpson
authors.forename: Simon
authors.initials: S
authors.lastname: Corbett
authors.forename: Alison
authors.initials: A
authors.lastname: Calver
authors.forename: John
authors.initials: J
authors.lastname: Morgan
authors.forename: Nick
authors.initials: N
authors.lastname: Curzen
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000601:surgery*; D003331:Coronary Vessels / Q000378:metabolism*; D054855:Drug-Eluting Stents; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011379:Prognosis; D011446:Prospective Studies; D013929:Thromboxane B2 / Q000097:blood; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D028761:Withholding Treatment
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D010975:Platelet Aggregation Inhibitors; D023201:CD40 Ligand; D013929:Thromboxane B2; D002097:C-Reactive Protein; D000077144:Clopidogrel; D013988:Ticlopidine