Identification of low responders to a 300-mg clopidogrel loading dose in patients undergoing coronary stenting.
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.
Angiolillo
Dominick J
DJ
Division of Cardiology, University of Florida, Shands Jacksonville, 655 West 8th Street, Jacksonville, FL 32209, USA. dominick.angiolillo@jax.ufl.edu
Fernandez-Ortiz
Antonio
A
Bernardo
Esther
E
Ramírez
Celia
C
Barrera-Ramirez
Carlos
C
Sabaté
Manel
M
Hernández
Rosana
R
Moreno
Raul
R
Escaned
Javier
J
Alfonso
Fernando
F
Bañuelos
Camino
C
Costa
Marco A
MA
Bass
Theodore A
TA
Macaya
Carlos
C
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
D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077144:Clopidogrel; D013988:Ticlopidine