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.


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.
Fontana
P
P
Division of Angiology and Hemostasis, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland.
Berdagué
P
P
Castelli
C
C
Nolli
S
S
Barazer
I
I
Fabbro-Peray
P
P
Schved
J-F
JF
Bounameaux
H
H
Mach
F
F
DE Moerloose
P
P
Reny
J-L
JL
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
D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin