Clinical predictors of dual aspirin and clopidogrel poor responsiveness in stable cardiovascular patients from the ADRIE study.

BACKGROUND: Poor response to both aspirin and clopidogrel (dual poor responsiveness [DPR]) is a major risk factor for recurrent ischemic events. OBJECTIVES: 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.

Biological effects of aspirin and clopidogrel in a randomized cross-over study in 96 healthy volunteers.

BACKGROUND: Some data suggest that biological 'resistance' to aspirin or clopidogrel may influence clinical outcome. OBJECTIVE: The aim of this study was to evaluate the relationship between aspirin and clopidogrel responsiveness in healthy subjects. METHODS: Ninety-six healthy subjects were randomly assigned to receive a 1-week course of aspirin 100 mg day(-1) followed by a 1-week course of clopidogrel (300 mg on day 1, then 75 mg day(-1)), or the reverse sequence, separated by a 2-week wash-out period. The drug effects were assessed by means of serum TxB2 assay, platelet aggregation tests, and the PFA -100 and Ultegra RPFA -Verify Now methods. RESULTS: Only one subject had true aspirin resistance, defined as a serum TxB2 level > 80 pg microL(-1) at the end of aspirin administration and confirmed by platelet incubation with aspirin. PFA-100 values were normal in 29% of the subjects after aspirin intake, despite a drastic reduction in TxB2 production; these subjects were considered to have aspirin pseudo-resistance. Clopidogrel responsiveness was not related to aspirin pseudo-resistance. Selected polymorphisms of platelet receptor genes were not associated with either aspirin or clopidogrel responsiveness. CONCLUSIONS: In healthy subjects, true aspirin resistance is rare and aspirin pseudo-resistance is not related to clopidogrel responsiveness.