The TIMI Risk Score for Unstable Angina/Non–ST Elevation MI

Context Patients with unstable angina/non–ST-segment elevation myocardial infarction (MI) (UA/NSTEMI) present with a wide spectrum of risk ... TheTIMIRiskScoreforUnstableAngina/Non–STElevationMI:AMethodforPrognosticationandTherapeuticDecisionMaking|AcuteCoronarySyndromes|JAMA|JAMANetwork Ourwebsiteusescookiestoenhanceyourexperience.Bycontinuingtouseoursite,orclicking"Continue,"youareagreeingtoourCookiePolicy | Continue [SkiptoNavigation] fulltexticon FullText contentsicon Contents figureicon Figures/Tables multimediaicon Multimedia attachicon SupplementalContent referencesicon References relatedicon Related commentsicon Comments DownloadPDF TopofArticle Abstract Methods Results Comment References Figure1.TIMIRiskScoreViewLargeDownloadRatesofall-causemortality,myocardialinfarction,andsevererecurrent ischemiapromptingurgentrevascularizationthrough14daysafterrandomization werecalculatedforvariouspatientsubgroupsbasedonthenumberofrisk factorspresentinthetestcohort(theunfractionatedheparingroupinthe ThrombolysisinMyocardialInfarction[TIMI]11Btrial;n=1957)(seeTable1).Eventratesincreasedsignificantly astheTIMIriskscoreincreased(P<.001by assessmentoftreatmenteffectaccordingtoscoreviewlargedownloadratesofall-causemortality ischemiapromptingurgentrevascularizationthrough14daysafterrandomization werecalculatedfortheenoxaparinandunfractionatedheparingroupsinthe thrombolysisinmyocardialinfarction safetyofsubcutaneousenoxaparininunstableanginaandnon-q-wavemitrial withincreasingtimiriskscorewasconfirmedinall3validationcohorts were0.65fortheunfractionatedheparingroupand0.61fortheenoxaparin groupintimi11b fortheenoxaparingroupinessence.therateofincreaseineventsasmore riskfactorswerepresentwassignificantlylowerintheenoxaparingroup inbothstudies favoringenoxaparin unfractionatedheparin.figure3.outcomesforindividualcomponents ofthecompositeprimaryendpointstratifiedbytimiriskscoreviewlargedownloadratesofall-causemortality revascularization afterrandomizationwerecalculatedfortheentirepopulationinthethrombolysis inmyocardialinfarction wasaprogressive pointasthetimiriskscoreincreased by shownwere0.74 and0.63 table1.baselinecharacteristicsanalyzed fordevelopmentoftimiriskscoreforua bytimiriskscore forfuturecontrolledtrials. practiceguideline10.3.calvin braunwaldclassification. andimpactofrecurrentischemia. diagnosishavetherapeuticimplications ontheemergencyroomelectrocardiogramineitherunstableanginapectoris ornon-q-wavemyocardialinfarctioninpredictingoutcome. withsuspectedunstablecoronaryheartdisease. basedondirectionandseverityofstsegmentdeviation. anginaandnon-qwavemyocardialinfarction:resultsofthetimiiiiregistry ecgancillarystudy. inunstablecoronaryarterydisease. inpatientswithacutecoronarysyndromes. ischemia. coronarysyndromestailoredtoclinicalpractice. oftreatmentefficacyinmeta-analysisofclinicaltrials. evaluationinthehospital. suggestiveofacutecardiacischemia:amulticenter myocardialinfarction. rapidtestingforcardiactroponintortroponini. relationtoserumtroponintlevels. withunstableanginaornon-qmyocardialinfarction:atimi11bsubstudy. myocardialinfarction:resultsofthethrombolysisinmyocardialinfarction forunstablecoronaryarterydisease. myocardialinfarction:timi11b-essencemeta-analysis. myocardialinfarction:resultsfromaninternationaltrialof41 withacutecoronarysyndromes. syndromes. intheemergencydepartment oflow-riskpatients. pharyngitis. patients. riskstratificationandtherapeuticdecisionmakinginacutecoronarysyndromes commentary august16 e.magnusohman continuingmedicaleducation seemoreabout acutecoronarysyndromesanticoagulationcardiologyischemicheartdisease selectyourinterests customizeyourjamanetworkexperiencebyselectingoneormoretopicsfromthelistbelow. acidbase addictionmedicine allergyandclinicalimmunology anesthesiology anticoagulation artandimagesinpsychiatry bleedingandtransfusion cardiology caringforthecriticallyillpatient challengesinclinicalelectrocardiography clinicalchallenge clinicaldecisionsupport clinicalimplicationsofbasicneuroscience clinicalpharmacyandpharmacology complementaryandalternativemedicine 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therationalclinicalexamination tobaccoande-cigarettes toxicology traumaandinjury treatmentadherence ultrasonography urology users vaccination venousthromboembolism veteranshealth violence women workflowandprocess woundcare savepreferences privacypolicy othersalsoliked thisissue citations viewmetrics downloadpdf twitter facebook more linkedin cite this citation antmanem downloadcitationfile: ris endnote bibtex medlars procite refworks referencemanager mendeley permissions originalcontribution thetimiriskscoreforunstableangina elliottm.antman carolynh.mccabe authoraffiliations authoraffiliations:cardiovasculardivision jama.2000 visualabstracticon visualabstract editorialcommenticon editorialcomment relatedarticlesicon relatedarticles authorinterviewicon interviews multimediaicon multimedia abstract context infarction andcardiacischemicevents.objective calculatedatpatientpresentation patientswithdifferentresponsestotreatmentsforua theefficacyandsafetyofsubcutaneousenoxaparininunstableanginaand non-q-wavemitrial patientswithua cohort respectivelyinessence.the3validationcohortsweretheunfractionated heparingroupfromessenceandbothenoxaparingroups.mainoutcomemeasures prognosticvariablesusingmultivariatelogisticregression valueof1whenafactorwaspresentand0whenitwasabsent thenumberoffactorspresenttocategorizepatientsintoriskstrata.relative differencesinresponsetotherapeuticinterventionsweredeterminedbycomparing theslopesoftheratesofeventswithincreasingscoreintreatmentgroups andbytestingforaninteractionbetweenriskscoreandtreatment.outcomes weretimiriskscorefordevelopingatleast1componentoftheprimaryend point requiringurgentrevascularization atleast3riskfactorsforcoronaryarterydisease of50 atleast2anginaleventsinprior24hours andelevatedserumcardiacmarkers.eventratesincreasedsignificantlyas thetimiriskscoreincreasedinthetestcohortintimi11b:4.7 of0 ofincreasingeventrateswithincreasingtimiriskscorewasconfirmedin all3validationgroups theincreaseineventrateswithincreasingnumbersofriskfactorswassignificantly lowerintheenoxaparingroupsinbothtimi11b interactionbetweentimiriskscoreandtreatment schemethatcategorizesapatient providesabasisfortherapeuticdecisionmaking. patientspresentingwithanacutecoronarysyndromewithoutst-segment elevationarediagnosedashavingunstableangina suchpatientshaveawidespectrumofriskfordeathandcardiacischemic events.1-5 manyattemptstoestimateagradientofriskamongpatientswithua focusonasinglevariable orelevatedserumcardiacmarkers.10-13 prognosticationschemeshavebeendevelopedthatcategorizepatients qualitativelyintohigh aquantitativestatementaboutfinergradationsofriskthatexistclinically.2althoughunivariateanalysesarein formativeasan initialassessmentoftheimportanceofapotentialprognosticvariable ofthecomplexprofileofpatientswithanacutecoronarysyndrome analysesthatadjustforseveralprognosticvariablessimultaneouslyprovide amoreaccuratetoolforriskstratification.2 reportsoftheresultsofrandomizedclinicaltrialsofnewtherapeutic strategiesforua ofatreatmentinapopulationthatisamixtureofpatientsatvaryingrisks oftheprimaryendpoint.althoughunivariatesubgroupanalysesarefrequently presentedinclinicaltrialreports oftheeffectofthenewtreatmentinagivensubgroupunlessadjustmentis madeforcovariates.giventhespectrumofclinicalpresentations thatthemagnitudeofthetreatmenteffectofatherapymayvarydepending ontheprofileofriskinanyspecificpatient.15 prognosticationofpatientrisk clinicianstotriagepatientstotheoptimumlocationfordeliveryofmedical care whomaybebestservedbypotentbutexpensive therapies.5 tofacilitatewidespreaduseofaprognosticscoringsystemforpatientswith ua arepartoftheroutinemedicalevaluationofsuchpatients. theprimarygoalofthisarticleistoreportthedevelopment andclinicalutilityofariskstratificationtoolforevaluationofpatients withua basedonage65yearsorolder markerssegregatedpatientswithua groups riskgroup.21however schemeusedonlyalimitednumberofbaselinecharacteristics.wedeveloped anew low-molecular-weightheparin toprovideatoolthatpotentiallycouldbeappliedinclinicalsettingsin whichpatientswithua methods thedesignandresultsofthetimi11bandefficacyandsafetyofsubcutaneous enoxaparininunstableanginaandnon-q-wavemi reportedpreviously.22 patients hoursofanepisodeofua atleast1ofthefollowing:st-segmentdeviationonthequalifyingecg transientstelevationorpersistentstdepressionof andelevatedserumcardiacmarkers. diseasewasacceptableinitiallybutwasdroppedlaterasthesolesupportive criterionforua in24hoursorless toanticoagulation. allpatientsreceivedaspirin informedconsent bothtrialsusedadoubledummytechniquesothatallpatientsreceivedboth anintravenousinfusion injections thetimiriskscoreforua fromtimi11bwasappliedtobothtrialsinafashionsimilartothatreported forthetimi11b thisendpointwasacompositeofall-causemortality orsevererecurrentischemiapromptingurgentrevascularization.theanalyses shownhereinarebasedonratesfortheprimaryendpointthrough14days afterrandomization. initially atleast1elementoftheprimaryendpointwasdeveloped.themodelincorporated baselinecharacteristicsthatcouldbereadilyidentifiedatpresentation andwasrestrictedtothecohortofpatientsassignedtounfractionatedheparin intimi11b informationthatcouldbeascertainedinarelativelyshortperiodafterencountering apatientandestablishingamodelthatcouldbeusedforefficienttriage forpatientcarewithoutwaitingforadditionaltestsorresultsofaninitial periodofmedicalobservationoverseveraldays.baselinecharacteristics thatwereevaluatedincludethosepreviouslyreportedtobeimportantvariables predictingoutcomesinpatientswithua atotalof12baselinecharacteristicsarrangedinadichotomousfashion werescreenedascandidatepredictorvariablesofriskofdevelopinganend-point event logisticregressionmodelwasthenusedtoassessthestatisticalsignificance ofeachcandidateprognosticvariable.aftereachfactorwastestedindependently inaunivariatelogisticregressionmodel levelofp multivariatestepwise associatedwithp model.maximumlikelihoodestimatesoftheparametercoefficientswereobtained usingsasproclogistic ofthemodeltotheobservedeventrateswasevaluatedbycalculatingthe hosmer-lemeshowstatistic.27low thehosmer-lemeshowstatisticindicatethatthedatacanbeadequatelyfit toalogisticfunction.theabilityofthemodeltoclassifypatients itspredictiveperformance totheareaunderareceiveroperatingcharacteristiccurvefordichotomous outcomes.28assessmentoftheimpactofmissing informationforpredictorvariableswascarriedoutbymonte-carlosimulations thatrandomlysetfixedproportionsofthedatatomissingandthenrepeating thelogisticregressionanalyses. afterdevelopmentofthemultivariatemodel beenfoundtobestatisticallysignificantpredictorsofeventsinthemultivariate analysis.thescorewasthenconstructedbyasimplearithmeticsumofthe numberofvariablespresent.differencesintheeventratesforincreasing timiriskscorevalueswereassessedusingthe trend. theriskscorewasthenvalidatedin3separatecohortsofpatients: theenoxaparingroupfromtimi11b groupfromessence intimi11bandessencebycomparingtheslopeoftheincreaseintherate ofeventswithincreasingtimiriskscoreusingleastsquareslinearregression analysis.differencesbetweentheunfractionatedheparinandenoxaparingroups inbothtimi11bandessencewerealsoassessedbycomparingtheslopeof theincreaseinrateofeventswithincreasingtimiriskscoreusingleast squareslinearregressionanalysis.inaddition thetimi11bandessencestudies stratifiedbyriskscorewascarriedoutbyexaminingthestatisticalsignificance oftheinteractionterminamultivariatelogisticregressionmodelofthe followingform:outcome="constant+riskscore+treatment(eg,unfractionated" heparinvsenoxaparin theasteriskinthemodeldesignatesaninteractionbetweentheadjoining terms.toexplorewhethertheinteractionofriskscore wasaffectedbythetrialinwhichthepatientwasenrolled statisticalsignificanceoftermsfortrial oftrialwithriskscoreandtreatmentwhenaddedtothemodel. asasecondarygoal topredictdevelopmentofeachoftheindividualcomponentsofthecomposite primaryendpointaswellasthecompositeendpointofall-causemortality ornonfatalmi. results thetestcohortfordevelopmentofthetimiriskscoreconsistedof the1957patientsassignedtoreceiveunfractionatedheparinintimi11b.22theprimaryendpoint urgentrevascularization testcohort.ofthe12originalcandidatevariables significantinthemultivariateanalysisandformedthefinalsetofpredictor variables statisticwas3.56df8 statisticforthemodelinthetestcohortwas0.65. sincetheparameterestimatesforeachofthe7predictorvariables wereofasimilarmagnitude theriskscorewascalculatedbyassigningavalueof1whenavariablewas presentandthencategorizingpatientsinthetestcohortbythenumberof riskfactorspresent becauseofthesmallnumberofpatientswithextremeriskscores with0or1riskfactor aprogressive scoreincreasedinthetestcohort inthefinalmodel valuewasclosetothemedianagefortheunfractionatedheparingroup years cutoffsshowedverylittleeffectonperformanceofthemodel:thecstatistic rangedbetween0.63and0.66forvaryingagecutoffsin5-yearincrements from50to80years.furthermore forthedevelopmentofasimpleriskscore performance:thecstatisticwas0.66inamodelusingageasacontinuous variable. oneofthe7predictorvariablesshownintable1 oftheresultsofapriorcardiaccatheterization.constructionofthetimi riskscoreusingthetimi11bdatabasewasaccomplishedfromthecasereport formdataforeachpatientand ofpriorcoronarystenosisof50 avalueof0wasassignedifnocardiaccatheterizationhadbeenpreviously performedorifapriorcardiaccatheterizationrevealednocoronarystenoses revealedatleast1coronarystenosisof50 sincetheresultsofapriorcardiaccatheterizationmightnotbeimmediately availabletoaclinicianattemptingtousethetimiriskscorewhenapatient valuesonthepriorcoronarystenosisof50 simulation morewasrandomlysetasmissing.themodelwasreevaluatedassuming0for missingpatientsandthenreevaluatedonceagainexcludingthemissingpatients. when10 asmissinganda0wasassumedforthemissingpatients priorcoronarystenosisof50 thecompositeoutcomeat14days:for10 for30 butexcludingmissingpatients assumptionsaboutmissingvalues asignificantpredictorofoutcome. validationofriskscore validationofthetimiriskscoreisshowninfigure2.theunfractionatedheparincontrolgroupsintimi11b andessenceshowedahomogeneouspatternwhenpatientswerestratifiedby riskscoresincetheslopeoftheincreaseineventrateswithincreasing numberofriskfactorswasnotstatisticallydifferent timi11b asthetimiriskscoreincreased applicationoftimiriskscore asshowninfigure2 relativerateofincreaseineventsamongpatientswithhighertimiriskscores wasdifferentfortheunfractionatedheparinandenoxaparingroups.forboth timi11bandessence numbersofriskfactorswassignificantlylowerintheenoxaparingroups vs6.41 increasingabsoluteriskdifferenceandcorrespondingdecreaseinthenumber ofpatientsrequiringtreatmenttoprevent1endpointeventby14daysafter randomizationfavoringenoxaparinwasseeninbothtrialsasthetimirisk scoreincreased. usingamergeddatabasefromthetimi11bandessencetrials multivariatelogisticregressionanalysisrevealedthatthetimiriskscore andtreatment mi asignificantpredictorofthecompositeoutcomeatday14 ofthecompositeoutcomeatday14:trial trial timiriskscore thelogisticregressionanalysishadnoeffectonoverallmodelperformance theabilityofthetimiriskscoretopredictoutcomesotherthanall-cause mortality entiretrialpopulation heparinandenoxaparingroupsintimi11bareshownintable2.forbothtreatmentgroups increaseintherateofeventsforeachoutcomewithincreasingriskscore. also riskscorewaslowerintheenoxaparingroup:68 comment ourresultsindicatethatstandardclinicalcharacteristicsroutinely obtainedduringtheinitialmedicalevaluationofpatientswithua canbeusedtoconstructasimpleclassificationsystemthatispredictive ofriskfordeathandcardiacischemicevents.thetimiriskscoreincludes variablesthatcanbeeasilyascertainedwhenapatientwithua tothemedicalcaresystem.thevariablesusedtoconstructthescorewere basedonobservationsfrompriorstudiesofriskstratificationandincorporate demographicandhistoricalfeaturesofthepatient andacuityofthepresentingillness ischemiaandnecrosis.2 thepredictorvariableswerederivedfromalogisticregressionmodelthat confirmedtheirindependentpredictivepoweraftermultivariateadjustment inthetimi11bandessencedatasets. thesimplearithmeticsumofthenumberofvariablespresentthatconstitutes theriskscorecanbecalculatedwithouttheaidofacomputer.thisdistinguishes thetimiriskscorefromotherscoringsystemsthataremorecomplexcomputationally sincetheyrequireweightingtermsforthepredictorvariablesandcannot beimplementedeasilywithoutcomputerassistance.25 theapproachtakenindevelopingthetimiriskscoreissimilartothattaken bycentoretal systemforassessmentofthelikelihoodofstreptococcalpharyngitisbased onclinicalfindingsascertainedintheemergencydepartment al ruleforidentifyingnervefunctionimpairmentinpatientswithleprosy. thetimiriskscoreappearsstatisticallyrobustinthatitwasvalidated internallywithintimi11baswellasin2separatecohortsofpatientsfrom theessencetrial.themodeliseasytorecallandapplyclinicallysince asimpleagecutoffof65yearsprovidedsimilarpredictiveabilitytoamore complexmodelusingageasacontinuousvariable.also knowledgeofwhetherthepatienthadapreviouslydocumentedcoronarystenosis remainedasignificantpredictorofevents. thetimiriskscoreoffersseveralpromisingapplicationsforclinical use.itcategorizespatientswithua ofriskforclinicalevents ofthetimiriskscorethathasnotbeenemphasizedinotherriskstratification studiesistheactualtestingofitsuseforidentifyingpatientswhowould beexpectedtoshowparticularbenefitfromnewantithromboticregimenssuch asenoxaparin.4asevidencedbythelowerslope oftheincreaseineventrateswithincreasingriskscoreinfigure2andthestatisticalsignificanceoftheinteracti onterm betweenriskscoreandtreatment thosepatientswithhighertimiriskscores.thatthelogisticregression modelingdidnotindicatethatthetrialinwhichthepatientwasenrolled wasapredictorofoutcomeandthattheinteractionsbetweentrialandrisk scorewerenotsignificantareconsistentwithanindependenteffectofenoxaparin acrossthe2trialsandillustratestheuseofthetimiriskscorefortherapeutic decisionmaking.theabsolutedifferenceineventratesincreasedandthe correspondingnumberofpatientsneededtotreatforpreventionof1event withenoxaparindecreasedastheriskscoreincreased atriskfortheindividualcomponentsofcompositeendpointsusedinmany contemporarytrialsoftherapiesforua ofagreatertreatmenteffectofenoxaparinwithincreasingriskscoreis notasstrongfortheindividualcomponentsasforthecompositeprimaryend point.thismayreflectlowerpowertodetectatreatmentbenefitfromenoxaparin duetolowerabsoluteeventratesfortheindividualelementsoftheendpoint althoughstatisticalsignificancefavoringenoxaparinwasobservedforall-cause mortalityandforurgentrevascularization severallimitationsofouranalysesshouldbeacknowledged.thetimi riskscorewasdevelopedincohortsofpatientswhoqualifiedforenrollment in2recentphase3trialsoftreatmentforua cohortsofpatientswhopresenttoemergencydepartmentsandphysicians withchestpainmustbeassessedtodetermineitsgeneralizabilitytoavariety ofclinicalsettings.theprecisenumericalrelationshipbetweenthetimi riskscoreandeventratesdescribedfortimi11bandessencemaybealtered astheriskscoreisappliedtootherpopulations.wedidnothavequantitative dataontheresultsofserumcardiacmarkers asadichotomousvariable.giventhequantitativerelationshipbetweenrelease ofcardiacbiomarkersandprognosis themodelcouldbeimprovedbyincorporatingaweightingtermforsmall andlargereleasesofbiomarkersdetectedatthetimeofpresentation.11 proteinmayprovideadditionalprognosticinformationandmayneedtobeincorporated infuturerefinementsoftheriskscoreassuchmeasurementsbecomemorewidely available.althoughintroductionofweightingfactorsforpredictorvariables orexpansionofthelistofpredictorvariablesmayleadtoimprovementin statisticalmeasuresofthepredictiveperformanceofthemodel thisislikelytooccuratthecostofalossofsimplicity.riskscoredevelopment requiresjudgmenttodeterminewhenamodelpredictsasufficientlylarge gradientofrisktobeclinicallyuseful producesunattractivelevelsofcomplexity. riskassessmentofpatientswithua initiallyinvolvesintegrationofdataatpresentationofthepatientand laterincorporateshospital-phasedatasuchastheresultsofnoninvasive andinvasivetesting andresponsetoinitialtherapeuticmaneuvers.4 atthetimeofinitialpresentation.updatingoftheriskscore databecomeavailable sincepatientswithanacutecoronarysyndromeareatincreasedrisk ofdeathandnonfatalcardiacevents anindividualbasistoformulateplansforevaluationandtreatment.thetimi riskscoreforua cliniciantocategorizeapatient atthecriticalinitialevaluation.apromisingclinicalapplicationofthis scoreisidentificationofapatientforwhomnewantithrombotictherapies wouldbeespeciallyeffective.otherconsiderationsmaybearonthedecision toprescribenewtherapies benefitmaybesmaller.finally theopportunityforevaluationofcost-effectivenessofotherdrugs asglycoproteiniib conservativestrategyinpatientswithanacutecoronarysyndrome. references x . accessyoursubscriptions signin accessthroughyourinstitution addorchangeinstitution freeaccesstonewlypublishedarticles createafreepersonalaccount toregisterforemailalerts purchaseaccess subscribetojournal getfulljournalaccessfor1year buyarticle getunlimitedaccessandaprintablepdf signinorcreateafreeaccount rentarticle rentthisarticlefromdeepdyve accesstofreearticlepdfdownloads saveyoursearch subscribenow customizeyourinterests createapersonalaccountorsigninto: registerforemailalertswithlinkstofreefull-textarticles accesspdfsoffreearticles manageyourinterests savesearchesandreceivesearchalerts makeacomment>