title: High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability.
abstract: OBJECTIVE
  To assess platelet inhibitory effects, interindividual variability in platelet inhibition as well as response to a 600 mg, compared to a standard 300 mg, clopidogrel loading dose (LD) after coronary stenting
  
  
  RESULTS
  Platelet function profiles were assessed in 50 patients undergoing coronary stenting receiving either a 300 mg (n=27) or 600 mg clopidogrel LD. ADP (6 microM) and collagen (6 microg/mL) induced platelet aggregation, as well as ADP (2 microM) induced glycoprotein (GP) IIb/IIIa activation and P-selectin expression were assessed at baseline and 4, 24, and 48 h following clopidogrel front-loading. A more intense and rapid inhibition of platelet activation (both GP IIb/IIIa activation and P-selectin expression) were achieved using a 600 mg, compared to a 300 mg, LD throughout the entire 48 hours (p<0.001). Although there were no differences in platelet aggregation, overall a 600 mg LD increased the number of clopidogrel responders and this was also achieved earlier compared to a 300 mg LD. A 600 mg LD did not reduce interindividual variability of platelet response.
  
  
  CONCLUSIONS
  The use of a 600 mg clopidogrel LD in patients undergoing coronary stenting optimises platelet inhibitory effects early after intervention and may provide a more effective protection against early thrombotic complications.
authors.affiliation: Division of Cardiology, University of Florida, Shands Jacksonville, 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: Fernández-Ortiz
authors.forename: Esther
authors.initials: E
authors.lastname: Bernardo
authors.forename: Celia
authors.initials: C
authors.lastname: Ramírez
authors.forename: Manel
authors.initials: M
authors.lastname: Sabaté
authors.forename: Camino
authors.initials: C
authors.lastname: Bañuelos
authors.forename: Rosana
authors.initials: R
authors.lastname: Hernández-Antolín
authors.forename: Javier
authors.initials: J
authors.lastname: Escaned
authors.forename: Raul
authors.initials: R
authors.lastname: Moreno
authors.forename: Fernando
authors.initials: F
authors.lastname: Alfonso
authors.forename: Carlos
authors.initials: C
authors.lastname: Macaya
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000601:surgery*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism; D012307:Risk Factors; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage* / Q000031:analogs & derivatives*
chemical_list: D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D040201:Platelet Membrane Glycoprotein IIb; D000077144:Clopidogrel; D013988:Ticlopidine