title: Impaired inhibition of P2Y(12) by clopidogrel is a major determinant of cardiac death in diabetes mellitus patients treated by percutaneous coronary intervention.
abstract: OBJECTIVE
  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.
authors.affiliation: Pôle d'Activité Médico-Chirurgicale Cardiovasculaire, Nouvel Hôpital Civil, Université de Strasbourg, France.
authors.forename: S
authors.initials: S
authors.lastname: El Ghannudi
authors.forename: P
authors.initials: P
authors.lastname: Ohlmann
authors.forename: L
authors.initials: L
authors.lastname: Jesel
authors.forename: B
authors.initials: B
authors.lastname: Radulescu
authors.forename: E
authors.initials: E
authors.lastname: El Adraa
authors.forename: U
authors.initials: U
authors.lastname: Crimizade
authors.forename: M L
authors.initials: ML
authors.lastname: Wiesel
authors.forename: C
authors.initials: C
authors.lastname: Gachet
authors.forename: O
authors.initials: O
authors.lastname: Morel
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000401:mortality*; D015815:Cell Adhesion Molecules / Q000097:blood; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000401:mortality / Q000628:therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000401:mortality*; D004351:Drug Resistance; D005260:Female; D005434:Flow Cytometry; D005602:France; D006331:Heart Diseases / Q000097:blood / Q000209:etiology / Q000401:mortality*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology / Q000401:mortality; D010750:Phosphoproteins / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects*; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000401:mortality; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C548576:P2RY12 protein, human; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D013988:Ticlopidine