| Objective: Platelet activation and aggregation play amajor role in acute coronary syndromes (ACS) and inthrombotic complications during and following percutaneouscoronary interventions (PCI). Antiplatelet therapy candramatically reduce ischemic complications. Clopidogrel is anew orally administered thienopyridine derivative thatselectively and irreversibly inhibits ADP-induced plateletaggregation. It has a favorable profile of side effects andexhibits faster antiplatelet activities, and has already been usedin patients with ACS and undergoing coronary stentimplantation. But a high variability occurred in the plateletinhibitory response to clopidogrel in patients with coronaryartery disease, some individual had weak response toclopidogrel, some subjects even have no response. Despiteintensified antiplatelet treatment, there were still some patientsundergoing coronary stenting developed thrombotic stentocclusion, suggesting incomplete platelet inhibition due toclopidogrel resistance. Muller found that 5% (ADP 5μmol/L)to 11% (ADP 20μmol/L) of the patients were non-respondersand 9% to 26% were semi-responders. Among the group ofnon-responders there were two incidents of subacute stentthrombosis after PCI. They also found that the incidence ofstent thrombosis was 1% to 5%, which was comparable to therate of clopidogrel non-responders (5%) when 5μmol/L ADPwas used to induce platelet aggregation. So they concluded thata subgroup of patients undergoing PCI did not adequatelyrespond to clopidogrel, which may correspond to theoccurrence of thromboischemic complications, and regardedthem as a higher-risk group. Jaremo also thought that those hadweak platelet response to clopidogrel were most likely havingan increased risk of thrombotic events. Therefore it was veryimportant to clarify the influential factor of clopidogrelresistance. Clopidogrel resistance also exists in healthy subjects.Lau found that among volunteers, 16% were clopidogrelnonresponders, 12% were low responders. Among patients,22% were nonresponders, 32% were low responders. Between20% and 30% of tested healthy subjects showed no significantinhibitory effect on measures of platelet reactivity afterclopidogrel was started. There were evidences that highpretreatment reactivity, Braunwald class 2 or 3 unstable angina(UA), statins use and hepatic Cytochrome P450 3A4 metabolicactivity were responsible for lower response to clopidogrel. Butthere were lack of study about the relation of baseline plateletactivation, thrombus formation and inflammatory state withclopidogrel resistance. Platelet membrane glycoprotein CD62Pand GPⅡb/Ⅲa were the specific markers of platelet activation.D-dimer was one molecular marker of ongoing thrombus andlysis. Hs-CRP was a inflammatory marker. The purpose of thepresent study was to find out the relationship between baselineplatelet activation, thrombus formation, the state ofinflammation and clopidogrel resistance by measuring plateletmembrane protein CD62P and membrane glycoprotein GPⅡb/Ⅲa, D-dimer and hs-CRP.Methods: 110 patients who administered clopidogrel (75mg QD) were enrolled between September 2003 and May 2004,including 84 males and 26 females, with a mean age of 58.81±11.83 years. Before clopidogrel administration bloodsamples were obtained through venipuncture so as to measurethe baseline levels of D-dimer, hs-CRP and the expression ofmembrane glycoprotein CD62P and GPⅡb/Ⅲa on the platelets.In addition, 4 days after clopidogrel administration, specimenswere obtained to measure the expression of CD62P and GPⅡb/Ⅲa on the platelets once more. According to the value changeof GP Ⅱb/ Ⅲa prior to and 4 days after clopidogreladministration, patients were divided into clopidogrelresistance group and non-clopidogrel resistance group. Alsoserum samples were obtained from ten inpatients, each samplewere divided into two shares to measure the expression of GPⅡb/Ⅲa. According the formula of x±1.96s, we got the valueof normal variation degree ranging from -0.54 to 1.38. So wedefined clopidogrel resistance as the higher 1.38% of changesof platelet GP Ⅱb/ Ⅲa expression after clopidogreladministration. Continuous variables were expressed as themean value±standard deviation(SD), categorical variableswere summarized as percentages. Independent-samples T testwas performed to determine the differences between meanvalues for continuous variables of baseline and concomitantcharacteristics between the two groups. Categorical variableswere compared using chi-square test. The influence of clinicalbaseline factors, concomitant medication, the markers ofplatelets activation, D-dimer and hs-CRP was evaluated bystepwise logistic regression analysis. A p value of <0.05 wasconsidered statistically significant.Results: Among the 110 patients, 25 (22.73%) patientshad clopidogrel resistance. The baseline characteristics such asage, weight, gender, smoking history, incidence ofhypercholesterolemia, hypertension, diabetes mellitus, historyof prior infarction, and the Braunwald unstable anginaclassification were not significantly different between the twogroups (P>0.05). The use of ACEIs and dihydropyridinecalcium channel blockers were more frequent in theclopidogrel resistance group, but the use of ACEIs was notstatistically significant when compared with thenon-clopidogrel resistance. A trend of higher nitrate use wasobserved in the non-clopidogrel resistance group (P<0.01).Other concomitant drug use did not differ significantly betweengroups (P>0.05). There were no significant differences betweenthe two groups with respect to baseline plasma level ofD-dimer and hs-CRP (all P>0.05). The patients in the...
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