Circulation. 2003;107:2908-2913
Published online before print June 9, 2003, doi: 10.1161/01.CIR.0000072771.11429.83
Published online before print June 9, 2003, doi: 10.1161/01.CIR.0000072771.11429.83
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(Circulation. 2003;107:2908.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Clopidogrel for Coronary Stenting
Response Variability, Drug Resistance, and the Effect of Pretreatment Platelet Reactivity
From the Sinai Center for Thrombosis Research (P.A.G., K.P.B., B.L.H.), Baltimore, Md, and Duke Clinical Research Institute (C.M.O.), Durham, NC.
Correspondence to Paul A. Gurbel, MD, Sinai Center for Thrombosis Research, Hoffberger Bldg, Suite 56, 2401 W Belvedere Ave, Baltimore, MD 21215. E-mail pgurbel{at}lifebridgehealth.org
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.
Key Words: drugs • platelets • stents
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