title: 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 600 mg of clopidogrel. The effect of clopidogrel was assessed using the VerifyNow assay 24 h 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 3.1 pg/ml, NR 5.7 pg/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.
authors.affiliation: Cardiocenter, 3rd Internal-Cardiology Clinic, 3rd Medical School, Charles University and University Hospital Kralovske Vinohrady, Srobarova 50, Prague, Czech Republic. pavel.osmancik@volny.cz
authors.forename: Pavel
authors.initials: P
authors.lastname: Osmancik
authors.forename: Petra
authors.initials: P
authors.lastname: Paulu
authors.forename: Petr
authors.initials: P
authors.lastname: Tousek
authors.forename: Viktor
authors.initials: V
authors.lastname: Kocka
authors.forename: Petr
authors.initials: P
authors.lastname: Widimsky
mesh_terms: D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D023201:CD40 Ligand / Q000097:blood; D000077144:Clopidogrel; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007249:Inflammation; D016753:Interleukin-10 / Q000097:blood*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D015415:Biomarkers; C508609:IL10 protein, human; D010975:Platelet Aggregation Inhibitors; D016753:Interleukin-10; D023201:CD40 Ligand; D000077144:Clopidogrel; D013988:Ticlopidine