TY - JOUR
T1 - Clopidogrel for coronary stenting
T2 - Response variability, drug resistance, and the effect of pretreatment platelet reactivity
AU - Gurbel, Paul A.
AU - Bliden, Kevin P.
AU - Hiatt, Bonnie L.
AU - O'Connor, Christopher M.
PY - 2003/6/17
Y1 - 2003/6/17
N2 - 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. Methods and Results - Platelet aggregation (5 and 20 μmol/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 (%) ≤10% by 5 μmol/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.
AB - 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. Methods and Results - Platelet aggregation (5 and 20 μmol/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 (%) ≤10% by 5 μmol/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.
KW - Drugs
KW - Platelets
KW - Stents
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UR - http://www.scopus.com/inward/citedby.url?scp=0038649988&partnerID=8YFLogxK
U2 - 10.1161/01.CIR.0000072771.11429.83
DO - 10.1161/01.CIR.0000072771.11429.83
M3 - Article
C2 - 12796140
AN - SCOPUS:0038649988
SN - 0009-7322
VL - 107
SP - 2908
EP - 2913
JO - Circulation
JF - Circulation
IS - 23
ER -