2010循环杂志残余血小板活性预测心血管风险(2)

CoronaryHeartDisease

CardiovascularDeathandNonfatalMyocardialInfarctioninAcuteCoronarySyndromePatientsReceivingCoronaryStentingArePredictedbyResidualPlateletReactivityto

ADPDetectedbyaPoint-of-CareAssay

A12-MonthFollow-Up

RossellaMarcucci,MD;AnnaMariaGori,BS;RitaPaniccia,BS;BettiGiusti,BS;

SerafinaValente,MD;CristinaGiglioli,MD;PiergiovanniBuonamici,MD;DavidAntoniucci,MD;

RosannaAbbate,MD;GianFrancoGensini,MD

Background—Theclinicalimpactofplateletaggregationassessedbypoint-of-careassaysisunknown.Wesoughttoevaluatewhetherhighresidualplateletreactivity(RPR)toADPduringclopidogreltherapy,measuredbyapoint-of-careassay,predictsadverseclinicaleventsinacutecoronarysyndromepatientsundergoingpercutaneouscoronaryintervention.

MethodsandResults—WeusedtheVerifyNowP2Y12assay(AccumetricsInc,SanDiego,Calif)todetermineRPRtoADPin683patientswithacutecoronarysyndromeundergoingdual-antiplatelettherapywhounderwentpercutaneouscoronaryinterventionwithbare-metalordrug-elutingstentimplantation.Allpatientsreceivedasingle600-mgclopidogrelloadingdosefollowedby75mgofclopidogreldailyand100to325mgofaspirindaily.Theendpointsofthestudyatfollow-upof12monthswerecardiovasculardeath,nonfatalmyocardialinfarction(MI),andtarget-vesselrevascularization.Ata12-monthfollow-up,wefound51ischemicevents(24cardiovasculardeaths[3.5%],27nonfatalMIs[3.9%])and40target-vesselrevascularizations(5.8%).Byreceiveroperatingcharacteristiccurve(ROC)analysis,theoptimalcutoffvalueinpredicting12-monthcardiovasculardeathandnonfatalMIwasP2Y12reactionunitvalues 240.RPR,definedinthepresenceofP2Y12reactionunitvaluesabovethiscutoff,wasfoundtobeasignificantandindependentpredictorofcardiovasculardeathandnonfatalMIinamodelthatadjustedforcardiovascularriskfactors,renalfailure,reducedleftventricularejectionfraction,multivesseldisease,totalstentlength,bifurcationlesions,numberoflesionstreated,typeofstent,anduseofglycoproteinIIb/IIIainhibitors(cardiovasculardeath:hazardratio2.55,95%CI1.08to6.07,P 0.034;nonfatalMI:hazardratio3.36,95%CI1.49to7.58,P 0.004).NosignificantassociationwasfoundbetweenhighRPRandtheriskoftarget-vesselrevascularization.

Conclusions—RPRtoADPwithclopidogreltherapy,measuredbythepoint-of-careassayVerifyNowP2Y12,isabletodetectacutecoronarysyndromepatientsatriskof12-monthcardiovasculardeathandnonfatalMI.Theoptimalcutoffvaluewasidentifiedasbeing240P2Y12reactionunits.(Circulation.2009;119:237-242.)

KeyWords:aspirinⅢclopidogrelⅢplateletsⅢbedsidetestingⅢacutecoronarysyndrome

ual-antiplatelettreatmentwithaspirinandclopidogrelinpatientsundergoingpercutaneouscoronaryintervention(PCI)hasdramaticallyreducedtherateofmajoradversecardiacevents.1,2Agrowingbodyofevidencedemonstratesthataninvitrohighresidualplateletreactivity(RPR)inpatientsundergoingdual-antiplatelettreatmentisassociatedwithanincreasedriskofadversecardiovasculareventssuchasstentthrombosisandcardiovasculardeath.3–8

D

ClinicalPerspectivep242

Clopidogrelnonresponsivenessasassessedbylighttrans-mittanceaggregometryinducedbyADP10 mol/Lisanindependentpredictorofdrug-elutingstent–implantationthrombosis.7Lighttransmittanceaggregometryisconsideredtobethestandardmethodforassessmentofplateletfunction,butlogisticproblemsmakeitsroutineusedifficult.Inrecent

ReceivedAugust6,2008;acceptedOctober23,2008.

FromtheDepartmentofMedicalandSurgicalCriticalCareandtheCenterfortheStudyattheMolecularandClinicalLevelofChronic,DegenerativeandNeoplasticDiseasestoDevelopNovelTherapies(R.M.,A.M.G.,R.P.,B.G.,R.A.,G.F.G.),UniversityofFlorence,Florence,Italy;DepartmentofHeartandVessels(R.M.,A.M.G.,R.P.,B.G.,S.V.,C.G.,P.B.,D.A.,R.A.,G.F.G.),AziendaOspedaliero-UniversitariaCareggi,Florence,Italy;andCentroS.MariaagliUlivi(G.F.G.),FondazioneDonCarloGnocchiOnlusIRCCS,Impruneta,Florence,Italy.

CorrespondencetoRossellaMarcucci,DepartmentofMedicalandSurgicalCriticalCare,UniversityofFlorence,UniversityofFlorence,VialeMorgagni85,50134FlorenceItaly.E-mailrossella.marcucci@unifi.it©2009AmericanHeartAssociation,Inc.Circulationisavailableat

DOI:10.1161/CIRCULATIONAHA.108.812636