Clopidogrel for coronary stenting: Response variability, drug resistance, and the effect of pretreatment platelet reactivity

Paul A. Gurbel, Kevin P. Bliden, Bonnie L. Hiatt, Christopher M. O'Connor

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2908-2913
Number of pages6
JournalCirculation
Volume107
Issue number23
DOIs
StatePublished - Jun 17 2003

Keywords

  • Drugs
  • Platelets
  • Stents

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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