Impaired inhibition of P2Y(12) by clopidogrel is a major determinant of cardiac death in diabetes mellitus patients treated by percutaneous coronary intervention

Atherosclerosis. 2011 Aug;217(2):465-72. doi: 10.1016/j.atherosclerosis.2011.03.039. Epub 2011 Apr 5.

Abstract

Objectives: We sought to determine whether low platelet response (LR) to the P2Y(12) receptor antagonist as assessed by vasodilator-stimulated phosphoprotein flow cytometry (VASP-FCT) differentially affects outcome in patients with or without diabetes mellitus undergoing percutaneous coronary intervention.

Background: While both DM and LR to clopidogrel are known to predict an unfavorable outcome after PCI, the deleterious effect of their association is less well established. The VASP-FCT is specific for the P2Y(12) ADP receptor pathway. In this test, platelet activation is expressed as the platelet reactivity index (PRI).

Methods: Patients were assigned to four different groups according to the presence or not of DM (DM, NDM) and LR to clopidogrel (LR, R). LR was defined as a PRI of >61%, a threshold previously identified as the optimal cut-off value to predict cardiac death following PCI.

Results: A total of 436 consecutive patients (163 DM, 273 NDM) were enrolled. The proportion of LR patients was higher in DM (47.9% vs. 35.2% p=0.011). At 9±2 months follow-up, the rates of total and cardiac mortality and possible and overall stent thrombosis were higher in DM-LR patients. Conversely, the cardiovascular outcome of DM-R patients was comparable to that of NDM (-LR or -R) patients. In DM, a multivariate analysis identified LR to clopidogrel (HR 6.09 [1.27-29.08], p=0.023) as the sole independent predictor of cardiac mortality.

Conclusions: In DM patients undergoing PCI, LR to clopidogrel is an independent predictor of cardiac death.

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary / adverse effects
  • Angioplasty, Balloon, Coronary / mortality*
  • Cell Adhesion Molecules / blood
  • Chi-Square Distribution
  • Clopidogrel
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / therapy*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / mortality*
  • Drug Resistance
  • Female
  • Flow Cytometry
  • France
  • Heart Diseases / blood
  • Heart Diseases / etiology
  • Heart Diseases / mortality*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Microfilament Proteins / blood
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / etiology
  • Myocardial Infarction / mortality
  • Phosphoproteins / blood
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests
  • Proportional Hazards Models
  • Prospective Studies
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Receptors, Purinergic P2Y12 / blood
  • Receptors, Purinergic P2Y12 / drug effects*
  • Registries
  • Risk Assessment
  • Risk Factors
  • Thrombosis / blood
  • Thrombosis / etiology
  • Thrombosis / mortality
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Time Factors
  • Treatment Outcome
  • Vasodilator-Stimulated Phosphoprotein

Substances

  • Cell Adhesion Molecules
  • Microfilament Proteins
  • P2RY12 protein, human
  • Phosphoproteins
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y12
  • Vasodilator-Stimulated Phosphoprotein
  • Clopidogrel
  • Ticlopidine