| Objective: Acute coronary syndrome (ACS) is caused by the rupture ofunstable atherosclerotic plaque and subsequent thrombosis, platelet activationand aggregation is at the core of its pathogenesis. Clopidogrel is a newthienopyridine substance and an adenosine diphosphate (ADP) receptor, and itcan combine with the ADP receptors on the surface of platelet membrane toinhibition the combining of fibrinogen and the glycoprotein Ⅱb/Ⅲa, as aresult, platelet aggregation is inhibited. Aspirin and clopidogrel are dualantiplatelet drugs of the treatment of ACS. When taken75mg/day in oral,clopidogrel achieves stable blood concentrations in3-7days. But there areindividual differences between the response to clopidogrel in ACS patients.Some patients present poor or no response to clopidogrel, and this is thephenomenon of clopidogrel resistance, which leads to a significant increase inthe incidence of thrombotic complications. Currently there is no unifiedstandard for the definition of clopidogrel resistance. At present the definitionproposed by Lau et al is more popular, which is defined that plateletaggregation is detected before and after clopidogrel treatment using ADP asinducer. Clopidogrel nonresponders, low responders, and responders weredefined by a relative inhibition of platelet aggregation of <10%,10%to29%,and≥30%, respectively.Mean platelet volume (MPV) is a commonly used indicator of plateletsize and the routine measurement of admitted hospital patients measured byautomated cell counting instrument, which is affordable and simple. Recentresearches found that elevated MPV can increase the risk of thromboticdiseases and be used as biological markers of platelet activation. The moreelevated of platelet volume, the more activated of platelet metabolism andenzyme, which lead to an increase in myocardial infarction mortality and restenosis after PCI, and it can be a prognostic indicator of ACS. Howeverthere hasn’t a result on the relationship of MPV and clopidogrel resistance, ifthe MPV can be an early prediction of clopidogrel resistance, it will play animportant role in regulating the antiplatelet drug of ACS. This aim of thisstudy is to find the relationship of MPV and the phenomenon of clopidogrelresistance, using the ROC curve to find a optimal cutoff point of MPV, inorder to provide guidance of antiplatelet drugs on the early step of ACS.Methods: A retrospective cohort study of this topic is carried, a total of207ACS patients between2006and2010in hospital was involved, whosebaseline and steady-state of platelet aggregation induced by10μmol/L and20μmol/L ADP has been detected already,140patients (67.6%) are male, and67patients (32.4%) are female, with the age of28-82years (59.1±10.1years).Collect the blood routine test within48hours of admission and generalclinical characters, according to the relative decreasing of platelet aggregation,the patients were divided into two groups, the clopidogrel nonresponder groupand responder group, according to the above-mentioned criteria. SPSS16.0software was used for statistical analysis. Measurement data showed a normaldistribution was described as mean±standard deviation (SD), and thecomparison between two groups was analyzed using two-sample t-test.Numerical data was expressed as rate (%), and the two groups were comparedusing Chi-square test or Fisher exact text. Risk factors for clopidogrelnonresponder were evaluated by logistic regression and ROC analysis wasused to determine the optimal cut-off points. A P value <0.05was consideredsignificant statistical difference.Results: Finally207patients were studied,140of them were male(67.6%),67patients were female (32.4%), aging28-82years (59.1±10.1years). When using10μmol/L ADP as an inducer, the clopidogrel respondergroup included171patients (82.6%), while clopidogrel nonresponder groupincluded36patients (17.4%). When using20μmol/L ADP as an inducer, thehe clopidogrel responder group included175patients (84.5%), clopidogrelnonresponder group included32patients (15.5%). The basic clinical characteristics and medication between the clopidogrel responders and theclopidogrel nonresponders showed no significant statistical difference. Using10μmol/L ADP as an inducer, MPV was8.13±1.36fl in the clopidogrelnonresponder group, and8.26±1.57fl in clopidogrel responder group, therewas no significant difference between two groups (P=0.608). Using20μmol/LADP as an inducer, MPV was8.28±1.58fl in the clopidogrel nonrespondergroup, and8.13±1.37fl in clopidogrel responder group, there was nosignificant difference between two groups (P=0.562). MPV was divided intodifferent groups according the quartile (Q1=7.3fl, Q2=7.9fl, Q3=8.9fl),using10μmol/L ADP as the inducer, the incidence of each group ofclopidogrel resistance was18.0%,17.3%,11.8%,22.2%respectively, therewas no significant difference (P=0.619).20μmol/L ADP as the inducer, theclopidogrel resistance rate in each group was16.0%,13.7%,15.7%,16.7%respectively, there was no significant difference (P=0.972).Using10μmol/L ADP as inducer, the optimal cut-off was8.75fldetermined by ROC curve analysis of PDW admitted to hospital within48hours, with a sensitivity of30.6%and a specificity of78.9%for identifyingclopidogrel nonresponder. The area under the curve is0.509(95%CI:0.399-0.619), P=0.866. Using20μmol/L ADP as inducer, the optimal cut-offwas10.55fl determined by ROC curve analysis of PDW admitted to hospitalwithin48hours, with a sensitivity of15.6%and a specificity of93.7%foridentifying clopidogrel nonresponder. The area under the curve is0.508(95%CI:0.397-0.618), P=0.889.Stepwise binary Logistic regression analysis was taken according to thepatient’s gender, age, the PLT, PDW, alcohol drinking, smoking, diabetes,hypertension, hyperlipidemia, stroke, the concomitant drugs use including PPI,statins, ACEI, ARB, CCB agents and MPV, which might be related toclopidogrel resistance. The results showed that the administration of ACEIwas a protective factor to clopidogrel resistance, OR=0.424(95%CI:0.202-0.894), P=0.024. Conclusion: MPVcannot be used to predict clopidogrel resistance. |
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