title: Impact of chronic kidney disease on platelet function profiles in diabetes mellitus patients with coronary artery disease taking dual antiplatelet therapy.
abstract: OBJECTIVE
  We sought to assess the impact of renal function on platelet reactivity in patients with diabetes mellitus (DM) and coronary artery disease on aspirin and clopidogrel therapy.
  
  
  BACKGROUND
  Diabetes mellitus is a key risk factor for chronic kidney disease (CKD). In aspirin-treated DM patients the presence of moderate/severe CKD is associated with reduced clinical efficacy of adjunctive clopidogrel therapy. Whether these findings may be attributed to differences in clopidogrel-induced effects is unknown.
  
  
  METHODS
  This was a cross-sectional observational study in which DM patients taking maintenance aspirin and clopidogrel therapy were studied. Patients were categorized into 2 groups according to the presence or absence of moderate/severe CKD. Platelet aggregation after adenosine diphosphate (ADP) and collagen stimuli were assessed with light transmittance aggregometry and defined patients with high post-treatment platelet reactivity (HPPR). Markers of platelet activation, including glycoprotein IIb/IIIa activation and P-selectin expression, were also determined using flow cytometry.
  
  
  RESULTS
  A total of 306 DM patients were analyzed. Patients with moderate/severe CKD (n = 84) had significantly higher ADP-induced (60 +/- 13% vs. 52 +/- 15%, p = 0.001) and collagen-induced (49 +/- 20% vs. 41 +/- 20%, p = 0.004) platelet aggregation compared with those without (n = 222). After adjustment for potential confounders, patients with moderate/severe CKD were more likely to have HPPR after ADP (adjusted odds ratio: 3.8, 95% confidence interval: 1.7 to 8.5, p = 0.001) and collagen (adjusted odds ratio: 2.4; 95% confidence interval: 1.1 to 5.4; p = 0.029) stimuli. Markers of platelet activation were significantly increased in patients with HPPR.
  
  
  CONCLUSIONS
  In DM patients with coronary artery disease taking maintenance aspirin and clopidogrel therapy, impaired renal function is associated with reduced clopidogrel-induced antiplatelet effects and a greater prevalence of HPPR.
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida 32209, USA. dominick.angiolillo@jax.ufl.edu
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: Esther
authors.initials: E
authors.lastname: Bernardo
authors.forename: Davide
authors.initials: D
authors.lastname: Capodanno
authors.forename: David
authors.initials: D
authors.lastname: Vivas
authors.forename: Manel
authors.initials: M
authors.lastname: Sabaté
authors.forename: José Luis
authors.initials: JL
authors.lastname: Ferreiro
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ueno
authors.forename: Pilar
authors.initials: P
authors.lastname: Jimenez-Quevedo
authors.forename: Fernando
authors.initials: F
authors.lastname: Alfonso
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Bass
authors.forename: Carlos
authors.initials: C
authors.lastname: Macaya
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernandez-Ortiz
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy*; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D012307:Risk Factors; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin