High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability.
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.
Angiolillo
Dominick J
DJ
Division of Cardiology, University of Florida, Shands Jacksonville, Jacksonville, FL 32209, USA. dominick.angiolillo@jax.ufl.edu
Fernández-Ortiz
Antonio
A
Bernardo
Esther
E
Ramírez
Celia
C
Sabaté
Manel
M
Bañuelos
Camino
C
Hernández-Antolín
Rosana
R
Escaned
Javier
J
Moreno
Raul
R
Alfonso
Fernando
F
Macaya
Carlos
C
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*
D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D040201:Platelet Membrane Glycoprotein IIb; D000077144:Clopidogrel; D013988:Ticlopidine