氯吡格雷治疗冠心病的几个问题与对策-魏盟

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1、氯吡格雷治疗冠心病的几个问题与对策上海市第六人民医院魏盟UFHADPADP受体抑制剂斑块破裂血管壁受损白血栓途径红血栓途径VonWillebrand因子、胶原血小板黏附血小板激活纤维蛋白原结合血小板聚集血栓凝血酶（IIa）组织因子/VIIa因子复合物LMWHXa纤维蛋白原纤维蛋白TXA2阿司匹林纤溶抗栓治疗GPIIb/IIIa受体拮抗剂PlateletStimuliGPIIb/IIIaintegrinADPEpinephrineCollagenThrombinPlateletAggregationSerotoninShearrateAATxA2COX-1ThrombinThrom

2、binThrombinTxA2TxA2ThrombinADPTXA2ADPP2Y12ADP(fibrinogenreceptor)GPIIb/IIIaActivationCOX-1clopidogrelbisulfateaspirincAMPOralAnti-PAR-1receptorsSCH530348E5555adaptedfromSchaferAI.AmJMed.1996;101:199-209.氯吡格雷治疗若干问题与对策用药时间、剂量、抵抗与新药氯吡格雷与PPI国产氯吡格雷循证学依据及其意义25,087ACSPatients(UA/NSTEMI70.8%,STEMI29.

3、2%)PlannedEarly(<24h)InvasiveManagementwithintendedPCIIschemicECGΔ(80.8%)or↑cardiacbiomarker(42%)PCI17,232(70%)Angio24,769(99%)NoPCI7,855(30%)NoSig.CAD3,616CABG1,809CAD2,430Randomizedtoreceive(2X2factorial):CLOPIDOGREL:Double-dose(600mgthen150mg/dx7dthen75mg/d)vsStandarddose(300mgthen75mg/d)A

4、SA:HighDose(300-325mg/d)vsLowdose(75-100mg/d)EfficacyOutcomes:CVDeath,MIorstrokeatday30StentThrombosisatday30SafetyOutcomes:CURRENTdefinedMajor/SevereandTIMIMajorKeySubgroup:PCIvNoPCIClopin1st7d(median)7d7d2d7dCompleteFollowup99.8%Compliance:DaysCumulativeHazard0.00.0040.0080.0120369121518212

5、42730ClopidogrelStandardDoseClopidogrelDoubleDose42%RRRHR0.5895%CI0.42-0.79P=0.001Clopidogrel:DoublevsStandardDoseDefiniteStentThrombosisDaysCumulativeHazard0.00.010.020.030.04036912151821242730Clopidogrel:DoublevsStandardDosePrimaryOutcome:PCIPatientsClopidogrelStandardClopidogrelDoubleHR0.8

6、595%CI0.74-0.99P=0.03615%RRRCVDeath,MIorStrokeDefiniteStentThrombosisin4Groups(AngiographicallyProven)DaysCumulativeHazard0.00.0040.0080.012036912151821242730CStandard,ALowCStandard,AHighCDouble,ALowCDouble,AHighStandardClopDoubleClopHRPPIntnHighASA1.20.60.490.003LowASA1.20.80.60.0580.35Clini

7、calImplicationsForevery1,000patientswithACSreceivingPCI,usingdouble-doseclopidogrelfor7daysinsteadofstandarddosewillpreventanadditional6MI’sand7stentthromboseswithanexcessof3severebleedsandnoincreaseinfatal,CABG-relatedorTIMImajorbleeds.Patie