title: Slow response to clopidogrel predicts low response.
abstract: OBJECTIVE
  The purpose of this study was to determine whether the speed of response to clopidogrel loading predicts the final degree of response.
  
  
  BACKGROUND
  Fast inhibition of platelet aggregation is important in the setting of acute coronary syndromes and percutaneous coronary intervention, but its association with the final degree of inhibition is not well established.
  
  
  METHODS
  We performed a post hoc analysis of the ALBION study; early kinetic profiles of adenosine diphosphate 20 micromol/l maximal platelet aggregation (MPA) and DeltaMPA (with baseline sample as reference) were studied at 8 time points within the 24 h after clopidogrel loading (300, 600, or 900 mg) in non-ST-segment elevation acute coronary syndrome patients. Low response was defined as DeltaMPA <10% over the first 24 h, fast response as DeltaMPA > or =10% at 1 h or before loading (the others being slow responders), and high post-treatment platelet reactivity as MPA > or =56.56% (fourth quartile). Inflammatory markers (PAC-1 and P-selectin) and vasodilator-stimulated phosphoprotein (VASP) were also evaluated according to onset of action.
  
  
  RESULTS
  Fifty-five percent of patients were slow responders. Noncurrent smoking and body mass index > or =25 kg/m(2) were associated with slower and lower responses. High post-treatment platelet reactivity was more frequent in slow responders (28% vs. 14%, p < 0.0001). There was a clopidogrel dose-effect relationship on DeltaMPA, with a trend toward faster onset of platelet inhibition in the 900-mg loading dose group. Slow responders had a slower and lower decrease in PAC-1 and P-selectin and higher VASP index at 6 h (76.5% vs. 66.4%, p = 0.019) and 24 h (70.3% vs. 61.5%, p = 0.049).
  
  
  CONCLUSIONS
  Slow response to clopidogrel, within the first hour of administration, is a reliable marker of low response at 24 h and high post-treatment platelet reactivity.
authors.affiliation: Assistance Publique Hôpitaux de Paris, Institut de Cardiologie, Pitié-Salpêtrière University Hospital, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Bellemain-Appaix
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: Johanne
authors.initials: J
authors.lastname: Silvain
authors.forename: Olivier
authors.initials: O
authors.lastname: Barthélémy
authors.forename: Farzin
authors.initials: F
authors.lastname: Beygui
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Collet
authors.forename: Georges
authors.initials: G
authors.lastname: Sideris
authors.forename: Catherine
authors.initials: C
authors.lastname: Meuleman
authors.forename: Claire
authors.initials: C
authors.lastname: Bal-Dit-Sollier
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lellouche
authors.forename: Grégory
authors.initials: G
authors.lastname: Ducrocq
authors.forename: Michel
authors.initials: M
authors.lastname: Slama
authors.forename: Olivier
authors.initials: O
authors.lastname: Milleron
authors.forename: Patrick
authors.initials: P
authors.lastname: Henry
authors.forename: Ludovic
authors.initials: L
authors.lastname: Drouet
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000244:Adenosine Diphosphate / Q000032:analysis; D000368:Aged; D054316:Biomarkers, Pharmacological / Q000032:analysis; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D054316:Biomarkers, Pharmacological; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine