title: Identification of low responders to a 300-mg clopidogrel loading dose in patients undergoing coronary stenting.
abstract: BACKGROUND
  Although patients undergoing coronary stenting routinely receive dual antiplatelet treatment to reduce the risk of stent thrombosis, this undesired event still occurs. A suboptimal response to clopidogrel treatment (low responders) has been suggested to contribute to stent thrombosis. In the present study, platelet function profiles were assessed in patients undergoing coronary stenting receiving a standard 300-mg clopidogrel loading dose with the aim to identify low clopidogrel responders.
  
  
  METHODS
  Platelet aggregation was assessed by light transmittance aggregometry following 6 microM ADP stimuli in 48 patients before and 10 min, 4 and 24 h after receiving clopidogrel front-loading. Patients having > or =40% inhibition of platelet aggregation 24 h after clopidogrel administration were defined as normal responders, whereas those having <40% inhibition were low responders. Glycoprotein (GP) IIb/IIIa activation and P-selectin expression were assessed by whole blood flow cytometry following 2 microM ADP stimuli at the same time points. Platelet function profiles were compared between normal and low clopidogrel responders.
  
  
  RESULTS
  Twenty-seven patients (56%) were normal responders and 21 (44%) low responders. Baseline GP IIb/IIIa activation was higher in low responders (74.6+/-16.6% vs. 58.2+/-24.5%, p=0.03). Although GP IIb/IIIa activation reduced following clopidogrel front-loading in both groups, it remained increased among low responders at 24 h (58.6+/-21.3% vs. 40.2+/-28.7%, p=0.05) and during the overall study time course (p=0.02). There were no differences in P-selectin expression.
  
  
  CONCLUSIONS
  A considerable proportion of patients have an early suboptimal response to a 300-mg clopidogrel loading dose. An increased GP IIb/IIIa activation before intervention may identify this group of patients suggesting the use of a more aggressive antithrombotic treatment in these individuals.
authors.affiliation: Division of Cardiology, University of Florida, Shands Jacksonville, 655 West 8th Street, Jacksonville, FL 32209, USA. dominick.angiolillo@jax.ufl.edu
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernandez-Ortiz
authors.forename: Esther
authors.initials: E
authors.lastname: Bernardo
authors.forename: Celia
authors.initials: C
authors.lastname: Ramírez
authors.forename: Carlos
authors.initials: C
authors.lastname: Barrera-Ramirez
authors.forename: Manel
authors.initials: M
authors.lastname: Sabaté
authors.forename: Rosana
authors.initials: R
authors.lastname: Hernández
authors.forename: Raul
authors.initials: R
authors.lastname: Moreno
authors.forename: Javier
authors.initials: J
authors.lastname: Escaned
authors.forename: Fernando
authors.initials: F
authors.lastname: Alfonso
authors.forename: Camino
authors.initials: C
authors.lastname: Bañuelos
authors.forename: Marco A
authors.initials: MA
authors.lastname: Costa
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Bass
authors.forename: Carlos
authors.initials: C
authors.lastname: Macaya
mesh_terms: D000368:Aged; D000077144:Clopidogrel; D003331:Coronary Vessels / Q000601:surgery*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000032:analysis; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011237:Predictive Value of Tests; D018570:Risk Assessment; D015607:Stents / Q000009:adverse effects*; D013927:Thrombosis / Q000209:etiology; D013988:Ticlopidine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077144:Clopidogrel; D013988:Ticlopidine