title: Association of estimated GFR with platelet inhibition in patients treated with clopidogrel.
abstract: BACKGROUND
  The reasons that decreased glomerular filtration rate (GFR) might alter the clinical efficacy of clopidogrel are poorly understood.
  
  
  METHODS
  In this study, we sought to evaluate whether decreased GFR alters platelet response to clopidogrel in patients receiving a maintenance dose of clopidogrel (75 mg/d for at least 8 days).
  
  
  METHODS
  126 consecutive patients categorized by estimated GFR: stages 1-2 (>60 mL/min/1.73 m(2); n = 29), stage 3a (45-59 mL/min/1.73 m(2); n = 21); stage 3b (30-44 mL/min/1.73 m(2); n = 26), stage 4 (15-29 mL/min/1.73 m(2); n = 14), and stage 5 (<15 mL/min/1.73 m(2); n = 36) were prospectively enrolled.
  
  
  METHODS
  Residual platelet reactivity, defined in the VASP (Vasodilator Stimulated Phosphoprotein) flow cytometry test as platelet reactivity index (PRI) ≥61% and in the VerifyNow turbidimetric-based assay as a value >235 PRU (adenosine diphosphate receptor reaction units) or percentage of platelet inhibition <15%.
  
  
  RESULTS
  We examined factors associated with low response to clopidogrel using logistic regression.
  
  
  RESULTS
  A significant relationship between estimated GFR, PRI, PRU, and percentage of inhibition was found. The prevalence of residual platelet reactivity was highest in patients with GFR stage 5. PRI ≥61% occurred in 52.8% of patients with stage 5 versus 30.8% of stage 3b and 24.1% of stages 1-2 (P = 0.1). PRU >235 was found in 63.6% of patients with stage 5 versus 36.8% of stage 3b and 17.2% of stages 1-2 (P = 0.005). Inhibition <15% affected 66.7% of patients with stage 5 versus 21.1% of stage 3b and 17.2% of stages 1-2 (P < 0.001). In the multivariable model, GFR stage 5 (adjusted prevalence ratio [PR], 3.10; 95% CI, 1.23-9.43; P = 0.02), and obesity (adjusted PR, 1.92; 95% CI, 1.34-2.23; P = 0.004) were the sole predictors of residual platelet reactivity.
  
  
  CONCLUSIONS
  Interference of hemodialysis with the pharmacokinetics of clopidogrel could not be excluded.
  
  
  CONCLUSIONS
  GFR stage 5 is associated with substantial impairment of platelet inhibition independently of diabetes mellitus.
authors.affiliation: Hôpitaux universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Muller
authors.forename: Sophie
authors.initials: S
authors.lastname: Caillard
authors.forename: Laurence
authors.initials: L
authors.lastname: Jesel
authors.forename: Soraya
authors.initials: S
authors.lastname: El Ghannudi
authors.forename: Patrick
authors.initials: P
authors.lastname: Ohlmann
authors.forename: Erik
authors.initials: E
authors.lastname: Sauleau
authors.forename: Thierry
authors.initials: T
authors.lastname: Hannedouche
authors.forename: Christian
authors.initials: C
authors.lastname: Gachet
authors.forename: Bruno
authors.initials: B
authors.lastname: Moulin
authors.forename: Olivier
authors.initials: O
authors.lastname: Morel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000077144:Clopidogrel; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010979:Platelet Function Tests; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000175:diagnosis* / Q000378:metabolism; D018570:Risk Assessment; D012720:Severity of Illness Index; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine