Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity.
BACKGROUND
Clopidogrel is administered to prevent stent thrombosis; however, the uniformity of platelet inhibition after treatment and the influence of pretreatment reactivity on drug response have not been described.


RESULTS
Platelet aggregation (5 and 20 micromol/L ADP), the activation of glycoprotein IIb/IIIa (PAC-1 antibody), and the expression of P-selectin were measured in patients undergoing elective coronary stenting (n=96) at baseline and at 2 hours, 24 hours, 5 days, and 30 days after stenting. All patients received aspirin (325 mg). Clopidogrel (300 mg) was administered in the catheterization laboratory and followed by 75 mg daily. There was marked interindividual variability in drug response as measured by all markers that showed a normal distribution. Resistance, defined as baseline aggregation (%) minus posttreatment aggregation (%) < or =10% by 5 micromol/L ADP, was present in 31% and 15% of patients at 5 and 30 days, respectively. Patients with the highest pretreatment platelet reactivity remained the most reactive at 24 hours after treatment (P<0.0001).


CONCLUSIONS
Interindividual variability in the platelet inhibitory response from clopidogrel occurs in patients undergoing elective coronary stenting. Patients with high pretreatment reactivity are least protected. Alternative pharmacological strategies and the association of adverse ischemic events should be investigated in these patients.
Gurbel
Paul A
PA
Sinai Center for Thrombosis Research, Hoffberger Bldg, Suite 56, 2401 W Belvedere Ave, Baltimore, Md 21215, USA. pgurbel@lifebridgehealth.org
Bliden
Kevin P
KP
Hiatt
Bonnie L
BL
O'Connor
Christopher M
CM
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D014644:Genetic Variation; D006801:Humans; D008297:Male; D019007:P-Selectin / Q000032:analysis / Q000096:biosynthesis; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects / Q000378:metabolism; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use*
D015415:Biomarkers; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin