2010循环杂志残余血小板活性预测心血管风险(3)

238CirculationJanuary20,2009

arrhythmia,orrefractorycongestiveheartfailure;2)nonfatalmyo-cardialinfarction(MI;ariseinserumtroponinIoranincreaseincreatinekinase-MBisoenzymeatleasttwicetheuppernormallimitswithatleast1ofthefollowing:acuteonsetofprolonged[ 20minutes]typicalischemicchestpain;ST-segmentelevationofatleast1mmin2ormorecontiguousECGleads,orST-segmentdepression 0.5mmin 2contiguousleads;orT-waveinversion 1mminleadswithpredominantRwaves);and(3)target-vesselrevascularizationbyrepeatPCIorCABG.

years,point-of-careassaysofplateletfunctionhavebecomeavailable,includingtheVerifyNowsystem,whichprovidesvaluesofRPRafterADPstimuluscorrelatedwiththosefoundbyADPlighttransmittanceaggregometry.9Onestudybasedon380patientsundergoingPCIandclopidogreltreat-menthasdemonstratedthathighADPRPR,asmeasuredbyVerifyNow,isassociatedwithpostdischarge(6-monthfollow-up)adverseeventsafterPCIwithdrug-elutingstents.8TheaimofthepresentstudywastoevaluatewhethertheVerifyNowassayisabletopredict12-monthclinicalrecur-rencesinalargesampleofpatientswithacutecoronarysyndrome(ACS)treatedbyPCI.

StatisticalAnalysis

Continuousvariablesarepresentedasmedian(range).Categoricaldataarereportedasfrequencies.DifferencesincontinuousvariableswerecomparedbytheStudentttestorMann–WhitneyUtest,asappropriate.Dichotomousvariableswerecomparedby 2testorFisher’sexacttest,asappropriate.

AreceiveroperatingcharacteristiccurveanalysiswasusedtodeterminetheabilityoftheVerifyNowP2Y12assaytodistinguishbetweenpatientswithandwithoutpostdischargeeventsafterPCI.Theoptimalcutoffpointwascalculatedbydeterminingthepost-treatmentPRUthatprovidedthegreatestsumofsensitivityandspecificity.CumulativesurvivalcurvesforpatientswithandwithouthighRPR(RPRasdefinedbyPRU 240)wereconstructedbytheKaplan–Meiermethod,andthelog-ranktestwasusedtoassessstatisticaldifferencesbetweenthese2survivalcurves.Afterassess-mentoftheproportionalhazardassumption,univariateandmulti-variatehazardregressionmodelsofCoxwereused,respectively,toidentifyriskfactorsforclinicalendpointsandtoadjustforpotentialconfoundersthatwereassociatedwithclinicalendpointsonunivar-iateanalysis(cardiovascularriskfactors,renalfailure,leftventricu-larejectionfraction 40%,multivesseldisease,totalstentlength,bifurcationlesions,numberoflesionstreated,typeofstentused,anduseofglycoproteinIIb/IIIainhibitors).

AsignificancelevelwasdefinedasP 0.05.AllanalysiswasperformedwithSPSS14.0(SPSSInc,Chicago,Ill).

Theauthorshadfullaccesstoandtakefullresponsibilityfortheintegrityofthedata.Allauthorshavereadandagreetothemanuscriptaswritten.

Methods

StudyPopulation

rmedwrittenconsentwasobtainedfromallpatients,andthestudywasapprovedbythelocalethicsreviewboard.

PCIandAntiplateletManagement

Allinterventionswereperformedaccordingtocurrentstandardguidelines,andthetypeofstentimplantedandtheuseofglycopro-teinIIb/IIIainhibitorswereatthediscretionoftheoperator.Allpatientsreceived1clopidogrelloadingdoseof600mgfollowedbyadailydoseof75mg.Allpatientsreceivedunfractionatedheparin70IU/kgduringtheprocedureandacetylsalicylicacid500mgIVfollowedbyadailydoseof100to325mgPO.

RPRAssessment

Venousbloodsamplesanticoagulatedwithsodiumcitrate0.109mol/L(ratio9:1)weretakenfromeachpatientwithin24hoursafter600-mgclopidogrelloading.ForpatientswhoreceivedboththeloadingdoseofclopidogrelandaglycoproteinIIb/IIIainhibitorinthecatheterizationlaboratory,bloodsampleswereobtained6daysafterward,whilethepatientwastakingthe75-mgmaintenancedoseofclopidogrel.

TheVerifyNowsystem(Accumetrics,SanDiego,Calif)isaturbidimetry-basedopticaldetectiondevicethatmeasuresplatelet-inducedaggregationinasystemcontainingfibrinogen-coatedbeads.Theinstrumentmeasureschangesinlighttransmissionandthustherateofaggregationinwholeblood.InthecartridgeoftheVerifyNowP2Y12assay,thereisachannelinwhichinhibitionoftheADPP2Y12receptorismeasured.ThischannelcontainsADPasplateletagonistandprostaglandinE1asasuppressorofintracellularfreecalciumlevels,toreducethenonspecificcontributionofADPbindingtoP2Y1receptors.ResultsareexpressedasP2Y12reactionunits(PRU).

Thereferenceintervalinasampleof98healthyvolunteersobtainedinourlaboratoryis244to382PRU(5thto95thpercentileofcontroldistribution,n 98).Samplesfrom5controlsubjectsand5coronaryarterydiseasepatientstakingdual-antiplatelettherapyandtheVerifyNowassaywetqualitycontrol(level1 normalandlevel2 abnormal)wereassessed4timestodetermineourlabora-torycoefficientofvariationfortheassay.Themeancoefficientsofvariationwere3.5%incontrolsubjects,3.2%incoronaryarterydiseasepatients,and2.5%and3.4%forlevel1and2qualitycontrols,respectively.9

Results

FromJanuary2005toMarch2006,683patientswereenrolledinthepresentstudy.Baselinecharacteristicsinclud-ingRPRareshowninTable1.PRUvalueswerenormallydistributed.Themeanplateletreactivitywas193.6 86.9PRU.Table2showsclinicaloutcomesat12months.The1-yearfollow-upratewas100%.Therewere51adverseevents:24cardiovasculardeaths(3.5%),27nonfatalMIs(3.9%),and40target-vesselrevascularizations(5.8%).

Receiveroperatingcharacteristiccurveanalysisdemon-stratedthatPRUwasabletodistinguishbetweenpatientswithandwithoutsubsequentischemicevents(namely,car-diovasculardeathsandnonfatalMI)at12-monthfollow-up(areaunderthecurve0.66,95%CI0.57to0.78,P 0.001;Figure1).Table3showsthattheadditionofRPRtoamodelthatincludedclassicandproceduralriskfactorsmoderatelybutsignificantlyimprovedtheareaunderthecurveforthedetectionof12-monthfollow-upcardiovasculardeathsandnonfatalMIs.APRU 240wasidentifiedastheoptimalcutofftopredictcardiovasculardeathandnonfatalMIat12-monthfollow-up,providingasensitivityof61%(95%CI47.0%to75.8%),aspecificityof70%(95%CI66.4%to73.5%),anegativepredictivevalueof96%(95%CI94.6%to98.0%),andapositivepredictivevalueof12%(95%CI0.7%to1.6%).PatientswithRPRPRUabovetheoptimalcutoffvalueweresignificantlyolder,morelikelytobefemale,more

DataCollectionandFollow-Up

Alldatawerecollectedprospectivelyandenteredintoacentraldatabase.Clinicalfollow-upinformationwasobtain …… 此处隐藏：4063字，全部文档内容请下载后查看。喜欢就下载吧 ……