Antiplatelet effects of clopidogrel and bleeding in patients undergoing coronary stent placement

J Thromb Haemost. 2010 Feb;8(2):250-6. doi: 10.1111/j.1538-7836.2009.03709.x. Epub 2009 Nov 28.


Background: In patients undergoing percutaneous coronary intervention (PCI), a link between bleeding and excess mortality has been demonstrated. A potential association of platelet response to clopidogrel and bleeding has not been well established yet.

Objectives: The aim of the present study was to assess the impact of clopidogrel responsiveness on the risk of bleeding in clopidogrel-treated patients undergoing PCI.

Methods: Patients (n=2533) undergoing PCI after pretreatment with 600 mg of clopidogrel were enrolled in this study. Blood was obtained directly before PCI. Adenosine-diphosphate (ADP)-induced platelet aggregation was assessed on a Multiplate analyzer. The primary endpoint was the incidence of in-hospital Thrombolysis in Myocardial Infarction (TIMI) major bleeding and the secondary endpoint was in-hospital TIMI minor bleeding. Receiver-operator curve (ROC) analysis was used to derive the optimal platelet aggregation value defining enhanced clopidogrel responders for the association of measurements with major bleeding.

Results: Thirty-four (1.3%) major bleeding events and 137 (5.4%) minor bleeding events were observed. The risk of a major bleeding was significantly higher in patients (n=975) with an enhanced response to clopidogrel as compared with the remaining patients (n=1558) (2.2 vs. 0.8%, unadjusted odds ratio (OR) 2.6, 95% confidence interval (CI) 1.3-5.2, P=0.005; adjusted OR 3.5, 95% CI 1.6-7.3, P=0.001). No significant differences between both groups were observed for the occurrence of minor bleeding events (P=0.68).

Conclusions: Enhanced clopidogrel responsiveness is associated with a higher risk of major bleeding. Whether guidance of antiplatelet treatment based on platelet function testing proves useful for avoiding bleeding events warrants further investigation.

Publication types

  • Multicenter Study

MeSH terms

  • Adenosine Diphosphate
  • Aged
  • Angioplasty, Balloon, Coronary / adverse effects
  • Angioplasty, Balloon, Coronary / instrumentation*
  • Chi-Square Distribution
  • Clopidogrel
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / therapy*
  • Drug-Eluting Stents*
  • Female
  • Germany
  • Hemorrhage / chemically induced*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / adverse effects*
  • Platelet Function Tests
  • Predictive Value of Tests
  • ROC Curve
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Thrombosis / blood
  • Thrombosis / etiology
  • Thrombosis / prevention & control*
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Time Factors
  • Treatment Outcome


  • Platelet Aggregation Inhibitors
  • Adenosine Diphosphate
  • Clopidogrel
  • Ticlopidine