Purpose. The aim was to identify factors that influence the efficacy of 600mg of clopidogrel pretreatment in patients with stable coronary artery disease (CAD) undergoing elective PCI.
Methods. In a laboratory substudy of the PRAGUE-8 trial, the influences of non-modifiable (age,sex) and modifiable (BMI,tobacco smoke) factors, co-morbidity (hypertension, hyperlipidemia,diabetes mellitus, renal insufficiency) and co-therapy (statin,aspirin,heparin) on the course of clopidogrel efficacy were investigated in 105 patients pretreated with clopidogrel ≥6h before coronary angiography±PCI. Flow cytometric analysis of the VASP phosphorylation state was used.
Results. There was no correlation between baseline platelet reactivity index (PRI) and severity of coronary atherosclerosis; mean PRI for a non-significant lesion 72±5.98% and for a significant lesion(s) 70.08±8.43%.The highest proportion of low-responders were diabetics (50% at 28h). Among tobacco smokers, the response to clopidogrel occurred quickly, and 80% of smokers had effective inhibition of PRI 12h after drug use. After adjustments, tobacco smoking was an independent predictor for the most robust drop of PRI 12h after clopidogrel (p=0.027). The magnitude of total decrease of PRI at 28h was not significantly influenced by cigarette smoking (p=0.12). Linear regression showed that patients on statin therapy had a better response to clopidogrel than those without statins (p=0.02).
Conclusion. In stable CAD, no correlation exists between baseline PRI and the severity and extent of coronary atherosclerosis. The 600mg of clopidogrel does not satisfactory suppress enhanced PRI in diabetics. Cigarette smoking is independently associated with a prompt antiplatelet response to clopidogrel. Ongoing statin therapy is an independent determinant of more effective clopidogrel-mediated inhibition of PRI.