拜糖蘋神內(nèi)科-沙龍會(huì)恢復(fù)期4-guidelines for the prevention of stroke patients with transient ischemic attack

GuidelinesforthePreventionofStrokeinPatientsWithStrokeorTransientIschemicAttack:AGuidelineforHealthcareProfessionalsFromtheAmericanHeartAssociation/AmericanStrokeAssociationKarenL.Furie,ScottE.Kasner,RobertJ.Adams,GregoryW.Albers,RuthL.Bush,SusanC.Fagan,JonathanL.Halperin,S.ClaiborneJohnston,IreneKatzan,WalterN.Kernan,PamelaH.Mitc,BruceOvbiagele,YukoY.Palesch,RalphL.Sacco,LeeH.Schwamm,SylviaWassertheil-Smoller,TanyaN.TuranandDeidreWentworthonbehalfoftheAmericanHeartAssociationStrokeCouncil,CouncilonCardiovascularNursing,CouncilonClinicalCardiology,andInterdisciplinaryCouncilonQualityofCareandesStroke.2011;42:227-276;originallypublishedonlineOctober21,:StrokeispublishedbytheAmericanHeartAssociation,7272GreenvilleAvenue,Dallas,TX75231Copyright?2010AmericanHeartAssociation,Inc.Allrights.PrintISSN:0039-2499.OnlineISSN:1524-Theonlineversionofthisarticle,alongwithupdatedinformationandservices,islocatedontheWorldWideWebat:DataSupplement(unedited)Permissions:Permissions:Requestsforpermissionstoreproducefigures,tables,orportionsofarticlesoriginallypublishedinStrokecanbeobtainedviaRightsLink,aserviceoftheCopyrightClearanceCenter,nottheEditorialOffice.Oncetheonlineversionofthepublishedarticleforwhichpermissionisbeingrequestedislocated,clickRequestPermissionsinthemiddlecolumnoftheWebpageunderServices.FurtherinformationaboutthisprocessisavailableinthePermissionsandRightsQuestionandAnswer Reprints:InformationaboutreprintscanbefoundonlineSubscriptions:InformationaboutsubscribingtoStrokeisonlineDownloadedfrombyguestonNovember19, AHA/ASA GuidelinesforthePreventionofStrokeinPatientsWithStrokeorTransientIschemicAttackAGuidelineforHealthcareProfessionalsFromtheAmericanHeartAssociation/AmericanStrokeAssociationTheAmericanAcademyofNeurologyaffirmsthevalueofthisguidelineasaneducationaltoolforneurologists.havereviewedthisandaffirmitseducationalcontent.KarenL.Furie,MD,MPH,FAHA,Chair;ScottE.Kasner,MD,MSCE,FAHA,ViceChair;RobertJ.Adams,MD,MS,FAHA;GregoryW.Albers,MD;RuthL.Bush,MD,MPH;SusanC.Fagan,PharmD,FAHA;JonathanL.Halperin,MD,FAHA;S.ClaiborneJohnston,MD,PhD;IreneKatzan,MD,MS,FAHA;WalterN.Kernan,MD;PamelaH.Mitc ,PhD,CNRN,RN,FAAN,FAHA;BruceOvbiagele,MD,MS,FAHA;YukoY.Palesch,PhD;RalphL.Sacco,MD,MS,FAHA,FAAN;LeeH.Schwamm,MD,FAHA;SylviaWassertheil-Smoller,MD,PhD,FAHA;TanyaN.Turan,MD,DeidreWentworth,MSN,RN;onbehalfoftheAmericanHeartAssociationStrokeCouncil,CouncilonCardiovascularNursing,CouncilonClinicalCardiology,andInterdisciplinaryCouncilonQualityofCareand esResearch—Theaimofthisupdatedstatementistoprovidecomprehensiveandtimelyevidence-based mendationsonthepreventionofischemicstrokeamongsurvivorsofischemicstrokeortransientischemicattack.Evidence-basedmendationsareincludedforthecontrolofriskfactors,interventionalapproachesforatheroscleroticdisease,antithrombotictreatmentsforcardioembolism,andtheuseofantiplaetagentsfornoncardioembolicstroke.Furthermendationsareprovidedforthepreventionofrecurrentstrokeinavarietyofotherspecificcircumstances,includingarterialdissections;patentforamenovale;hyperhomocysteinemia;hypercoagulablestates;sicklecelldisease;cerebralvenoussinusthrombosis;strokeamongwomen,particularlywithregardtopregnancyandtheuseofpostmenopausalhormones;theuseofanticoagulationaftercerebralhemorrhage;andspecialapproachestoimplementationofguidelinesandtheiruseinhigh-riskpopulations.(Stroke.2011;42:227-:AHAScientific transientischemic strokeTheAmericanHeartAssociationmakeseveryefforttoavoidanyactualorpotential sofinterestthatmayariseasaresultofanoutsiderelationshipora al,professional,orbusinessinterestofamemberofthewritingpanel.Specifically,allmembersofthewritinggrouparerequiredtocompleteandsubmitaDisclosureQuestionnaireshowingallsuchrelationshipsthatmightbeperceivedasrealorpotentialsofinterest.ThisguidelinewasapprovedbytheAmericanHeartAssociationScienceAdvisoryandCoordinatingCommitteeonJuly13,2010.Acopyoftheguidelineisavailableatbyselectingeitherthe“topiclist”linkorthe“chronologicallist”link(No.KB-0102).Topurchaseadditionalreprints,call ore-mailkelleramsay Theonline-onlyDataSupplementisavailable TheAmericanHeartAssociationrequeststhatthis becitedasfollows:FurieKL,KasnerSE,AdamsRJ,AlbersGW,BushRL,FaganSC,HalperinJL,JohnstonSC,KatzanI,KernanWN,MitcPH,OvbiageleB,PaleschYY,SaccoRL,SchwammLH,Wassertheil-SmollerS,TuranTN,WentworthD;onbehalfoftheAmericanHeartAssociationStrokeCouncil,CouncilonCardiovascularNursing,CouncilonClinicalCardiology,andInterdisciplinaryCouncilonQualityofCareand esResearch.Guidelinesforthepreventionofstrokeinpatientswithstrokeortransientischemicattack:aguidelineforhealthcareprofessionalsfromtheAmericanHeartAssociation/AmericanStrokeAssociation.Stroke.2011;42:227–276.ExpertpeerreviewofAHAScientificStatementsisconductedattheAHANationalCenter.FormoreonAHAstatementsandguidelinesdevelopment,visit.Permissions:Multiplecopies,modification,alteration,enhancement,and/ordistributionofthis arenotpermittedwithouttheexpresspermissionoftheAmericanHeartAssociation.Instructionsforobtainingpermissionarelocatedat identifier4431.Alinktothe“PermissionRequestForm”appearsontherightsideofthepage.?2010AmericanHeartAssociation,Strokeisavailableat :10.1161/STR.0b013e3181f7d043StrokeisamajorsourceofmortalityandmorbidityintheSorstrokerepresentapopulationatincreasedriskofsubsequentstroke.Approximayonequarterofthe795000strokesthatisdifficulttogaugebecausealargeproportionofpatientswhoexperienceaTIAfailtoreportittoahealthcareprovider.1Onthebasisofepidemiologicaldatadefiningthedeterminantsofderiveevidence-based mendationstoreducestrokerisk.Notably,muchoftheexistingdatacomefromstudieswithlimitednumbersofolderadults,women,anddiverseethnicalizabilityofthepublishedfindings.Theaimofthisstatementistoprovideclinicianswiththemostup-to-dateevidence-based mendationsforthepreventionofischemicstrokeamongsurvivorsofischemicstrokeorTIA.AwritingcommitteechairandvicechairweredesignatedbytheStrokeCouncilManuscriptOversightCommittee.AwritingcommitteerosterwasdevelopedandapprovedbytheStrokeCouncilwithrepresentativesfromneurology,cardiology,radiology,surgery,nursing,phar-macy,andepidemiology/biostatistics.Thewritinggroupconductedacomprehensivereviewandsynthesisoftherelevantliterature.Thecommitteereviewedallcompiledreportsfromcomputerizedsearchesandconductedadditionalsearchesbyhand.Thesesearchesareavailableonrequest.SearcheswerelimitedtoEnglish-languagesourcesandhu-mansubjects.LiteraturecitationsweregenerallyrestrictedtopublishedmanuscriptsappearinginjournalslistedinIndexMedicusandreflectedliteraturepublishedasofAugust1,2009.Becauseofthescopeandimportanceofcertainongoingclinicaltrialsandotheremerginginformation,pub- swerecitedforinformationalpurposeswhentheyweretheonlypublishedinformationavailable,butmendationswerenotbasedon salone.Thereferencesselectedforthisareexclusivelyforpeer-reviewedpapersthatarerepresentativebutnotall-inclusive,withprioritygiventoreferenceswithhigherlevelsofevidence.Allmembersofthecommitteehadfrequentopportunitiestoreviewdraftsoftheandreachaconsensuswiththefinal tionsfollowtheAmericanHeartAssociation(AHA)andtheAmericanCollegeofCardiology(ACC)methodsofclassi-fyingthelevelofcertaintyofthetreatmenteffectandclassofevidence(Tables1andAlthoughpreventionofischemicstrokeistheprimaryeofinterest,manyofthegradesforthe dationswerechosentoreflecttheexistingevidenceonthereductionofallvascular subsequentstroke,myocardialinfarction(MI),andvasculardeath.The mendationsinthisstatementareorganizedtohelptheclinicianwhohasarrivedatapotentialexplanationofthecauseofischemicstrokeinanindividualpatientandisembarkingonselectionofatherapytoreducetheriskofarecurrenteventandothervascular updatethesestatementsevery3years,withadditionalintervaltheapproachestopreventarecurrent

DefinitionofTIAandIschemicStrokeSubtypesATIAisanimportantpredictorofstroke.The90-dayriskofstrokeafteraTIAhasbeenreportedasbeingashighas17%,withthegreatestriskapparentinthefirstweek.3,4ThedistinctionbetweenTIAandischemicstrokehas elessimportantinrecentyearsbecausemanyofthepreventiveapproachesareapplicabletoboth.5TIAandischemicstrokesharepathophysiologicmechanisms,butprognosismayvarydependingonseverityandcause,anddefinitionsaredepen-dentonthetimingandextentofthediagnosticevaluation.Byconventionalclinicaldefinitions,thepresenceoffocalneu-rologicalsymptomsorsignslasting24hourshasbeendefinedasaTIA.Withmorewidespreaduseofmodernimagingtechniquesforthebrain,uptoonethirdofpatientswithsymptomslasting24hourshavebeenfoundtohaveaninfarction.5,6Thishasledtoanewtissue-baseddefinitionofTIA:atransientepisodeofneurologicaldysfunctioncausedbyfocalbrain,spinalcord,orretinalischemia,withoutacuteinfarction.5Notably,themajorityofstudiesdescribedinthisguidelineusedtheolderdefinition. mendationspro-videdbythisguidelinearebelievedtoapplytobothstrokeandTIAregardlessofwhichdefinitionisused.Theclassificationofischemicstrokeisbasedonpresumedmechanismofthefocalbraininjuryandthetypeandlocalizationofthevascularlesion.Theclassiccategorieshavebeendefinedaslarge-arteryatheroscleroticinfarction,whichmaybeextracranialorintracranial;embolismfromacardiacsource;small-vesseldisease;otherdeterminedcausesuchasdissection,hypercoagulablestates,orsicklecelldisease;andinfarctsofundeterminedcause.7Thecertaintyofclassificationoftheischemicstrokemechanismisfarfromidealandreflectstheinadequacyofthediagnosticworkupinsomecasestovisualizetheoccludedarteryorlocalizethesourceoftheembolism.Thesettingofspecific dationsforthetimingandtypeofdiagnosticworkupforpatientswithTIAorstrokeisbeyondthescopeoftheseguidelines;atabareminimum,allstrokepatientsshouldhavebrainimagingwithcomputedtomographyormagneticreso-nanceimaging(MRI)todistinguishbetweenischemicandhemorrhagicevents,andbothTIAandischemicstrokepatientsshouldhaveanevaluationsufficienttoexcludehigh-riskmodifiableconditionssuchascarotidstenosisoratrialfibrillation(AF)asthecauseofischemicsymptoms.RiskFactorControlforAllPatientsWithTIAorIschemicStrokeAnestimated72millionAmericanshavehypertension,de-finedasasystolicbloodpressure(BP)140mmHgordiastolicBP90mmHg.8Overall,thereisanassociationbetweenbothsystolicanddiastolicBPandriskofstrokewithoutaclearthresholdevenatasystolicBPof115mmHg.9Meta-ysesofrandomizedcontrolledtrialshaveshownthatBPloweringisassociatedwitha30%to40%reductioninriskofstroke.10–12RiskreductionisgreaterwithlargerreductionsinBPwithoutclearevidenceofadrugclass–specifictreatmenteffect.12Evidence- *Dataavailablefromclinicaltrialsorregistriesabouttheusefulness/efficacyindifferentsubpopulations,suchasgender,age,historyofdiabetes,historyofpriormyocardialinfarction,historyofheartfailure,andprioraspirinuse.AmendationwithLevelofEvidenceBorCdoesnotimplythatthemendationisweak.Manyimportantclinicalquestionsaddressedintheguidelinesdonotlendthemselvestoclinicaltrials.Eventhoughrandomizedtrialsarenotavailable,theremaybeaveryclearclinicalconsensusthataparticulartestortherapyisusefuloreffective. mendations(ClassIandIIa;LevelofEvidenceAandBonly)regardingthecomparativeeffectivenessofonetreatmentwithrespecttoanother,thesewordsorphrasesmaybe paniedbytheadditionalterms“inpreferenceto”or“tochoose”toindicatethefavoredintervention.Forexample,“TreatmentAismendedinpreferencetoTreatmentBfor…”or“ItisreasonabletochooseTreatmentAoverTreatmentBfor….”StudiesthatsupporttheuseofcomparatorverbsshouldinvolvedirectcomparisonsofthetreatmentsorstrategiesbeingdationsforBPscreeningandtreatmentof swithhypertensionaresummarizedintheAmericanStrokeAsso-ciation(ASA)GuidelinesonthePrimaryPreventionofIschemicStroke13andaredetailedintheSeventhReportoftheJointNationalCommitteeonPrevention,Detection,Evaluation,andTreatmentofHighBloodPressure(JNC7).14JNC7stressestheimportanceoflifestylemodificationsinthemanagementofhypertension.Lifestyleinterventionsassoci-atedwithreductionofBPincludeweightloss(includingsaltrestriction);theconsumptionofadietrichinfruits,vegeta-bles,andlow-fatdairyproducts;regularaerobicphysicalactivity;andlimitedalcoholconsumption.14Althoughnumerousrandomizedtrialsandmeta-ysestionofprimarycardiovasculardiseaseingeneralandstrokein

secondarypreventionamong swithstrokeorTIA.10,15ThereisagenerallackofdefinitivedatatohelpguidetheimmediatemanagementofelevatedBPinthesettingofacuteischemicstroke;acautiousapproachhasbeen andtheoptimaltimetoinitiatetherapyremainsuncertain.16Ameta-ysisofrandomizedtrialsshowedthatantihy-pertensivemedicationsreducedtheriskofrecurrentstrokeafterstrokeorTIA.15Themeta-ysisincluded7random-izedtrialsperformedthrough2002:theDutchTIAtrial(atenolol,a-blocker),17PoststrokeAntihypertensiveTreat-mentStudy(PATS;indapamide,adiuretic),18Heart esPreventionEvaluation(HOPE;ramipril,anangioten-sin-convertingenzymeinhibitor[ACEI]),19andPerindoprilProtectionAgainstRecurrentStrokeStudy(PROGRESS;3othersmallertrials.21–23Togetherthesetrialsincluded15527Table2.DefinitionofClassesandLevelsofEvidenceUsedin ClassClassConditionsforwhichthereisingevidenceand/oradivergenceofopinionabouttheusefulness/efficacyofaprocedureortreatmentClassTheweightofevidenceoropinionisinfavoroftheprocedureorClassUsefulness/efficacyislesswellestablishedbyevidenceorClassConditionsforwhichthereisevidenceand/orgeneralagreementthattheprocedureortreatmentisnotuseful/effectiveinsomecasesmaybeLevelofEvidenceA Dataderivedfrommultiplerandomizedclinicaltrialsormeta-ysesLevelofEvidenceB DataderivedfromasinglerandomizedtrialornonrandomizedstudiesLevelofEvidenceC Consensusopinionofexperts,casestudies,orstandardofcare LevelofEvidenceA DataderivedfrommultipleprospectivecohortstudiesusingareferencestandardappliedbyamaskedevaluatorLevelofEvidenceB DataderivedfromasinglegradeAstudy,oroneormorecase-controlstudies,orstudiesusingareferencestandardappliedbyanunmaskedLevelofEvidence Consensusopinionoftheeffectsofnonpharmacologicalinterventions.Overall,treatmentwithantihypertensivedrugswasassoci-atedwithsignificantreductionsinrecurrentstrokes(relativerisk[RR],0.76;95%confidenceinterval[CI],0.63toMI(RR,0.79;95%CI,0.63to0.98),andallvascular(RR,0.79;95%CI,0.66to0.95).15Theimpactofreductionwassimilarintherestrictedgroupofsubjectswithhypertensionandwhenallsubjects,includingthosewithandwithouthypertension,wereyzed.LargerreductionsinsystolicBPwereassociatedwithgreaterreductioninriskofrecurrentstroke.Thesmallnumberoftrialslimitedcompar-isonsbetweenantihypertensivemedications.Significantre-ductionsinrecurrentstrokewereseenwithdiureticsaloneandincombinationwithACEIsbutnotwith-blockersorACEIsusedalone;nonetheless,statisticalpowerwaslimited,particularlyfortheassessmentof-blockers,andcalciumchannelblockersandangiotensinreceptorblockerswerenotevaluatedinanyoftheincludedtrials.Sincethismeta-ysis,2additionallarge-scalerandom-izedtrialsofantihypertensivemedicationsafterstrokehavebeenpublished:MorbidityandMortalityAfterStroke,Epro-sartanComparedwithNitrendipineforSecondaryPrevention(MOSES),24andPreventionRegimenforEffectivelyAvoid-ingSecondStrokes(PRoFESS).25InMOSES,1405subjectswithhypertensionandastrokeorTIAwithintheprior2yearswererandomizedtoeprosartan(anangiotensinreceptorblocker)ornitrendipine(acalciumchannelblocker).24BPreductionsweresimilarwiththe2agents.TotalstrokesandTIAs(countingrecurrentevents)werelessfrequentamongthoserandomizedtoeprosartan(incidencedensityratio,0.75;95%CI,0.58to0.97),andtherewasareductionintheriskofprimarycompositeevents(death,cardiovascularevent,orcerebrovascularevent;incidencedensityratio,0.79;95%0.66to0.96).AreductioninTIAsaccountedformostofthebenefitincerebrovascularevents,withnosignificantdiffer-enceinischemicstrokes,andamoretraditionalysisof

timetofirstcerebrovasculareventdidnotshowabenefitofeprosartan.InPRoFESS,20332subjectswithischemicstrokewererandomlyassignedtomisartanorplacebowithin90daysofanischemicstroke.25misartanwasnotassociatedwithareductioninrecurrentstroke(hazardratio[HR],0.95;95%CI,0.86to1.04)ormajorcardiovascularevents(HR,0.94;95%CI,0.87to1.01)duringmean2.5-yearfollow-up.TheBP-loweringarminPRoFESSwasstatisti-callyunderpowered.NonadherencetomisartanandmoreaggressivetreatmentwithotherantihypertensivemedicationsintheplacebogroupreducedthedifferenceinBPbetweenthetreatmentgroups(systolicBPdifferedby5.4mmHgat1monthand4.0mmHgat1year)andmayhavereducedtheimpactoftreatmentonstrokerecurrence.Takentogether,aparticularroleforangiotensinreceptorblockersafterstrokehasnotbeenconfirmed.BPreductionis mendedforbothpreventionofrecurrentstrokeandpreventionofothervasculareventsin swhohavehadanischemicstrokeorEvidenceA).Becausethisbenefitextendsto outa edhistoryofhypertension,this strokeorTIAwhoareconsideredappropriateforBPreduction(ClassIIa;LevelofEvidenceB).AnabsolutetargetBPlevelandreductionareun-certainandshouldbeindividualized,butbenefithasbeenassociatedwithanaveragereductionofap- y10/5mmHg,andnormalBPlevelshavebeendefinedas<120/80mmHgbyJNC7(ClassIIa;LevelofEvidenceB).SeverallifestylemodificationshavebeenassociatedwithBPreductionandareareasonablepartofacomprehensiveantihypertensivetherapy(ClassIIa;LevelofEvidenceC).Thesemodificationsincludesaltrestriction;weightloss;consumptionofadietrichinTable mendationsforTreatableVascularRiskRisk BPreductionis mendedforbothpreventionofrecurrentstrokeandpreventionofothervasculareventsinBecausethisbenefitextendsto swithandwithoutaedhistoryofhypertension,thismendationisreasonableforallpatientswithischemicstrokeorTIAwhoareconsideredappropriateforBPreduction(ClassIIa;LevelofEvidenceAnabsolutetargetBPlevelandreductionareuncertainandshouldbeindividualized,butbenefithasbeenassociatedwithanaveragereductionofapproximay10/5mmHg,andnormalBPlevelshavebeendefinedas120/80mmHgbyJNC7(ClassIIa;LevelofEvidenceSeverallifestylemodificationshavebeenassociatedwithBPreductionandareareasonablepartofacomprehensiveantihypertensivetherapy(ClassIIa;LevelofEvidenceC).Thesemodificationsincludesaltrestriction;weightloss;consumptionofadietrichinfruits,vegetables,andlow-fatdairyproducts;regularTheoptimaldrugregimentoachievethe mendedlevelofreductionisuncertainbecausedirectcomparisonsbetweenregimensarelimited.TheavailabledataindicatethatdiureticsorthecombinationofdiureticsandanACEIareuseful(ClassI;LevelofEvidenceA).Thechoiceofspecificdrugsandtargetsshouldbeindividualizedonthebasisofpharmacologicalproperties,mechanismofaction,andconsiderationofspecificpatientcharacteristicsforwhichspecificagentsareprobablyindicated(eg,extracranialcerebrovascularocclusivedisease,renalimpairment,cardiacdisease,anddiabetes)(ClassIIa;LevelofEvidenceB).(New UseofexistingguidelinesforglycemiccontrolandBPtargetsinpatientswithdiabetesis mendedforpatientswhohavehadastrokeorTIA(ClassI;LevelofEvidenceB).(New Statintherapywithintensivelipid-loweringeffectsis eventsamongpatientswithischemicstrokeorTIAwhohaveevidenceofatherosclerosis,anLDL-Clevel100mg/dL,andwhoarewithoutknownCHD(ClassI;LevelofEvidenceB).ForpatientswithatheroscleroticischemicstrokeorTIAandwithoutknownCHD,itisreasonabletotargetareductionofatleast50%inLDL-CoratargetLDL-Clevelof70mg/dLtoobtainumbenefit(ClassIIa;LevelofEvidenceB).(Newmendation)PatientswithischemicstrokeorTIAwithelevatedcholesterolorcomorbidcoronaryarterydiseaseshouldbeotherwisemanagedaccordingtoNCEPIIIguidelines,whichincludelifestylemodification,dietaryguidelines,and mendations(ClassI;LevelofEvidenceA).PatientswithischemicstrokeorTIAwithlowHDL-Cmaybeconsideredfortreatmentwithniacinor(ClassIIb;LevelofEvidence

ClassI;LevelAClassIIa;LevelClassIIa;LevelClassIIa;LevelClassIIa;LevelClassI;LevelBClassIIa;LevelClassIIb;LevelCHDindicatescoronaryheartdisease;HDL,high-densitylipoproteincholesterol;LDL-C,low-densitylipoproteincholesterol;NCEPIII,TheThirdReportoftheNationalCholesterolEducationProgramExpertPanelonDetection,Evaluation,andTreatmentofHighCholesterolinAdults;andSPARCL,StrokePreventionbyAggressiveReductioninCholesterol.*SeeTables1and2forexplanationofclassandlevelofaerobicphysicalactivity;andlimitedalcoholTheoptimaldrugregimentoachievethe mendedlevelofreductionisuncertainbecausedirectdiureticsandanACEIareuseful(ClassI;LevelofEvidenceA).Thechoiceofspecificdrugsandtargetsofspecificpatientcharacteristicsforwhichspecificagentsareprobablyindicated(eg,extracranialcere-B).(New mendation;Table3)Diabetesisestimatedtoaffect8%oftheadultpopulationintheUnitedStates.26Prevalenceis15%to33%inpatientswithischemicstroke.27–29Diabetesisaclearriskfactorforfirststroke,30–34butthedatasupportingdiabetesasariskfactor

forrecurrentstrokearemoresparse.Diabetesmellitusap-pearstobeanindependentpredictorofrecurrentstrokeinpopulation-basedstudies,35and9.1%ofrecurrentstrokeshavebeenestimatedtobeattributabletodiabetes.36,37Dia-beteswasapredictorofthepresenceofmultiplelacunarinfarctsin2strokecohorts.38,39Normalfastingglucoseisdefinedasglucose100mg/dL(5.6mmol/L),andimpairedfastingglucosehasbeendefinedasafastingplasmaglucoseof100mg/dLto125mg/dL(5.6mmol/Lto6.9mmol/L).26Afastingplasmaglucose126mg/dL(7.0mmol/L),orA1C6.5%,oracasualplasmaglucose200mg/dL(11.1mmol/L)inthesettingofsymptomsattributabletohyperglycemiameetsthethresholdforthediagnosisofdiabetes.26AhemoglobinA1c(HbA1c)level7%isdefinedasinadequatecontrolofDiet,exercise,oralhypoglycemicdrugs,andinsulinaremendedtogainglycemiccontrol.26Threemajorrandomizedclinicaltrialsofintensiveglucosemanagementin swithdiabeteswithahistoryofcardiovasculardisease,stroke,oradditionalvascularfactorshaveallfailedtodemonstrateareductionincardio-vasculareventsordeathinthegroupsreceivingintensiveglucosetherapy.IntheActiontoControlCardiovascularRiskinDiabetes(ACCORD)trial,10251patientswithtype2diabetesandvasculardiseaseormultipleriskfactorswererandomlyassignedtoanintensivetreatmentprogramtarget-ingaglycohemoglobinlevelof6%versusastandardprogramwithagoalHbA1clevelof7%to7.9%.39Thetrialwashaltedafterameanof3.5yearsoffollow-upbecauseofanincreasedriskofdeathinpatientsrandomizedtotheintensivetreatmentprogram(HR,1.22;95%CI,1.01to1.46).Therewasnosignificantdifferenceintherateofnonfatalstroke(HR,1.06;95%CI,0.75to1.50;P0.72)orintheprimaryendpoint,whichwasacompositeofnonfatalheartattack,nonfatalstroke,anddeathduetoacardiovascu-larcause(HR,0.90;95%CI,0.78to1.04;P0.16).ActioninDiabetesandVascularDisease(ADVANCE)trialalsofailedtoshowabenefitinsecondarypreventionofcardiovascularevents.Inthistrial11140patientswithtype2diabetesandahistoryofmacrovasculardiseaseoranotherriskfactorwererandomlyassignedtointensiveglucosecontrol(target6.5%)orstandardglucosecontrol(targetHbA1c7%).40Thirty-twopercentofsubjectshadahistoryofmajormacrovasculardisease,including9%withahistoryofstroke.Therewasnosignificantreductionintheoccur-renceofmacrovasculareventsalone(HR,0.94;95%CI,0.84to1.06;P0.32)ornonfatalstroke(3.8%inbothtreatmentarms).IncontrasttotheACCORDtrial,therewerenosignificantdifferencesintherateofdeathsbetweenthestudygroups.Finally,theVeteransAffairsDiabetesTrial,consist-ingof1791veteranswithtype2diabetesassignedtointensivebloodglucosetreatmentorstandardtreatment,foundnosignificantdifferencebetweenthe2groupsinanycomponentoftheprimary e,whichconsistedoftimetooccurrenceofamajorcardiovascularevent,orintherateofdeathduetoanycause(HR,1.07;95%CI,0.81to1.42;P0.62).40TheresultsofthesetrialsindicatetheglycemictargetsshouldnotbeloweredtoHbA1c6.5%inpatientswithahistoryofcardiovasculardiseaseorthepresenceofvascularriskfactors.AmongpatientswhohavehadastrokeorTIAanddiabetes,guidelineshavebeenestablishedforglycemiccontrol41andBPmanagement.14Recentlytheuseofpioglitazonehasbeenevaluatedin5238patientswithtype2diabetesandmacrovasculardisease.InthePROspectivepioglitAzoneClinicalTrialInmacroVas-cularEvents(PROactive),therewasnosignificantreductionintheprimaryendpointofall-causedeathorcardiovasculareventsinpatientsrandomlyassignedtopioglitazonecom-paredwithplacebo(HR,0.78;95%CI,0.60to1.02).42,43Remarkably,amongpatientswhoenteredPROactivewithahistoryofstroke,pioglitazonetherapywasassociatedwitha47%relativeriskreductioninrecurrentstroke(HR,0.53;95%CI,0.34to0.85),anda28%relativeriskreductioninstroke,MI,orvasculardeath(HR,0.72;95%CI,0.53to1.00).Conversely,rosiglitazone,anotherofthethiazo-lidinedioneclassofdrugs,hasbeenlinkedtotheocc