title: Clinical predictors of dual aspirin and clopidogrel poor responsiveness in stable cardiovascular patients from the ADRIE study.
abstract: BACKGROUND
  Poor response to both aspirin and clopidogrel (dual poor responsiveness [DPR]) is a major risk factor for recurrent ischemic events.
  
  
  OBJECTIVE
  The aim of this study was to identify factors associated with DPR, defined with specific tests, and derive a predictive clinical score.
  
  
  METHODS
  We studied 771 consecutive stable cardiovascular patients treated with aspirin (n = 223), clopidogrel (n = 111), or both drugs (n = 37). Aspirin responsiveness was evaluated by serum thromboxane (Tx)B₂ assay, and clopidogrel responsiveness by calculating the platelet reactivity index (PRI) on the basis of the phosphorylation status of the vasodilator phosphoprotein. The analysis was focused on patients treated with both drugs, and on independent predictors of DPR.
  
  
  RESULTS
  Among patients on dual therapy, there was no relevant correlation between TxB₂ levels and PRI values (r = 0.11). Sixty-seven patients (15.4%) had DPR. Diabetes [odds ratio (OR) 1.89, 95% confidence interval (CI) 1.06-3.39], high body weight (> 86 kg vs. < 77 kg, OR 4.74, 95% CI 2.49-9.73), low aspirin dose (75-81 mg vs. ≥ 160 mg, OR 0.12, 95% CI 0.09-0.93) and high C-reactive protein (CRP) level (> 1.6 mg L⁻¹ vs. < 0.6 mg L⁻¹, OR 3.66, 95% CI 1.74-8.72) were independently associated with DPR, via increased TxB(2) levels, increased PRI, or both. These associations with TxB₂ and PRI were reproduced across the whole population. With use of a factor-weighed score (c-index = 0.74), the predicted prevalence of DPR was 57% in the highest strata of the score as compared with < 4% for the lowest strata.
  
  
  CONCLUSIONS
  Diabetes, body weight, the aspirin dose and CRP levels are readily available independent predictors of DPR, and some are potential targets for reducing its prevalence.
authors.affiliation: Division of Angiology and Hemostasis, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Fontana
authors.forename: P
authors.initials: P
authors.lastname: Berdagué
authors.forename: C
authors.initials: C
authors.lastname: Castelli
authors.forename: S
authors.initials: S
authors.lastname: Nolli
authors.forename: I
authors.initials: I
authors.lastname: Barazer
authors.forename: P
authors.initials: P
authors.lastname: Fabbro-Peray
authors.forename: J-F
authors.initials: JF
authors.lastname: Schved
authors.forename: H
authors.initials: H
authors.lastname: Bounameaux
authors.forename: F
authors.initials: F
authors.lastname: Mach
authors.forename: P
authors.initials: P
authors.lastname: DE Moerloose
authors.forename: J-L
authors.initials: JL
authors.lastname: Reny
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011379:Prognosis; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin