Identification of low responders to a 300-mg clopidogrel loading dose in patients undergoing coronary stenting

Thromb Res. 2005;115(1-2):101-8. doi: 10.1016/j.thromres.2004.07.007.


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.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Clopidogrel
  • Coronary Vessels / surgery*
  • Female
  • Humans
  • Male
  • Middle Aged
  • P-Selectin / analysis
  • Platelet Activation / drug effects
  • Platelet Aggregation / drug effects
  • Platelet Function Tests
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Predictive Value of Tests*
  • Risk Assessment
  • Stents / adverse effects*
  • Thrombosis / etiology
  • Ticlopidine / administration & dosage*
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology


  • P-Selectin
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Clopidogrel
  • Ticlopidine