High leukocyte count and interleukin-10 predict high on-treatment-platelet-reactivity in patients treated with clopidogrel

Abstract

According to recent trials, a significant number of patients do not have a completely effective response to clopidogrel. The aim of the study was to evaluate the rate of clopidogrel resistance in the context of important clinical characteristics and to specifically determine the relation between clopidogrel efficacy and biomarkers of inflammation. Consecutive non-selected patients following PCI were enrolled into the study. All patients received a loading dose of 600mg of clopidogrel. The effect of clopidogrel was assessed using the VerifyNow assay 24h after clopidogrel administration, clopidogrel resistance was defined as PRU≥240. At the same time, standard parameters of biochemistry and hematology, the concentration of anti-inflammatory cytokine interleukin-10 and of soluble CD40 ligand, were measured. 378 patients were enrolled. 243 (64.3%) patients were responders (R) and 135 patients (35.7%) were non-responders (NR). Non-responders were older (R 65.7±13.3, NR 69.8±11.5, P<0.05), had a higher prevalence of diabetes (R 26.3%, NR 38.5%, P<0.05), were more often on mechanical ventilation (R 0.8%, NR 4.4%, P<0.05). The leukocyte count (R 9.8±3.5, NR 11.7±12.8, P<0.05), and concentration of IL-10 (R 3.1pg/ml, NR 5.7pg/ml, P<0.05) was higher among non-responders. The concentration of CD40L was not significantly different between the groups. In a multivariate logistic regression, older age, higher weight, female gender, mechanical ventilation, and a higher concentration of leukocytes and IL-10 were associated with an increased risk for being a non-responder. Older, obese patients, especially women had a higher risk of high on-treatment-platelet-reactivity. Higher concentrations of leukocytes and interleukin-10 were also an important factor associated with the risk of low clopidogrel responsiveness.