The Influence Of Rosuvastatin Or Simvastatin On Antiplatelet Function Of Clopidogrel

Objective:1. To explore the effection of different kinds of statins unit clopidogrel on the acutecardial syndrome (ACS) patients’ platelet function,by means of determing the plateletaggregation rate before and after taking Rosuvastatin or Simvastatin and clopidogrel.2. To explore the relationship between the gene polymorphism of CYP2C19and theantiplatelet effects of clopidegrel.Methods:Elected one hundred patients admitted in Liaocheng secend people hospital betweenOctober2010and January2012who fit the acute cardial syndrome diagnosis standard.Exclusion standard:(1) The patients with family genetic or personal hemorrhagic disease;(2)The patients whose international standardization ratio>2.0,prothrombin time1.5timesgreater than the normal range;(3) The patients whose blood tests show Hb <90g/L,plateletcount>450×109/L or <100×109/L;(4) Patients older than90years old or younger than18years old;(5) Patients with a recent malignant tumor,or serious diseases of the blood,orcardiac function level IV (NAYA hierarchical) or severe insufficiency of liver andkidney;(6) Patients tabooing on tclopidogrel,aspirin,low molecular weight heparin (lowmolecular heparin,LMWH);(7) Patients taking prilosec,statins,clopidogrel and drugs nearly1weeks;(8) Patients had a recent surgery or be suspected aortic dissection.All the patients who accord with the conditions above were divided into two groupsby the digital random table (R group and S group),both groups were given clopidogrel(Sanofi pharmaceutical Co.,LTD),take75mg/d to maintain after taken300mg at adraught.R group were given rosuvastatin (Simcere pharmaceutical Co.,LTD)10mg/d,betaken at bedtime; Group S were given simvastatin (Merck pharmaceutical Co.,LTD)40mg/d,be taken at bedtime,the rest therapies of the two groups are carried through accordingto the conventional treatment scheme (this therapeutic schedule eliminated drugs strictlywhich have been confirmed metabolizing via the CYP3A4or CYP2C9metabolic pathway,such as calm drugs,proton pump inhibitors and warfarin).Take venous blood oftwo groups respectively before combine medication,24hours and7days (at this time theirbody clopidogrel concentration has reach a steady state)after the combinationadministration,determine platelet aggregation rate (PAR) induced by the5umol/L ADPusing platelet aggregation analyzer,within one hour after blood taken.Divide all the patientsinto two groups according to the variation of platelet aggregation rate (PAR)7days afterdrug taken: clopidogrel resistance group (group A) and the clopidogrel resistance group(group B),the platelet aggregation rate before taking drugs platelet aggregation rate afterdrug taken,if the sent do not greater than ten percent,we defined the condition asclopidogrel resistance(CR).In group B,we select patients at random with equal number asgroup A for group C,then go on with determining the CYP2C19genotype in group A andC.All data are processed by SPSS13.0software,among them,P <0.05means thedifferences are significant.Result:Patients’ platelet aggregation rate (PAR)%before drug combination,24hours and7days after combine medication respectively is:52.71±17.64、43.85±14.50、38.75±10.51.Ingroup R.The platelet aggregation rate (PAR)%before drug combination,24hours and7days after combine medication respectively is:49.02±16.80、41.05±13.76、37.72±10.43.Theplatelet aggregation rate in the Two groups has no statistical difference (P>0.05) beforecombination administration.Patients’ platelet aggregation are significantly depressed24hours after combine medication in the two groups.But the platelet aggregation rate24hours after drug combination has no statistical difference between the two groups (P>0.05),so does the platelet aggregation rate7days after combination administration.This experiment screened out15cases which are clopidogrel resistance (groupA),among their CYP2C19genotype,8cases are CYP2C19*1/*1(636GG,681GG),3casesare CYP2C19*1/*2(636GG,681GA),1case is CYP2C19*1/*3(636GA,681GG),2casesare CYP2C19*2/*2(636GG,681AA),and1case is CYP2C19*2/*3(636GA,681GA).Among the CYP2C19genotypes of patients who are selected in thenonresistance group (group C),9patients are CYP2C19*1/*1(636GG,681GG),4patientsare CYP2C19*1/*2(636GG,681GA),and2patients are CYP2C19*2/*2(636GG,681AA),the most common CYP2C19*1/*1、CYP2C19*1/*2and CYP2C19*1/*3are fastmetabolism type,CYP2C19*2/*2、 CYP2C19*3/*3and CYP2C19*2/*3are slowmetabolism type,there are12fast metabolism cases and3slow metabolism cases in group A,13fast metabolism cases and2slow metabolism cases in group C,there are no statisticaldifference between the two groups (P>0.05).Conclusion:1. Both Rosuvastatin which metabolized via CYP2C9pathway and Simvastatinmetabolizing via CYP3A4pathway have no obvious influence on the clopidogrelantiplatelet effects,do not even increase the incidence of clopidogrel resistance.2. The CYP2C19gene types has no significant relationship with the clopidogrelantiplatelet rate,and all the patients diagnosised as acute cardial syndrome can takeclopidogrel according to the guidelines recommended dose,no matter which CYP2C19genotype he is.