顱內動脈粥樣硬化相關RCT試驗

顱內動脈粥樣硬化狹窄治療

相關RCT試驗三個提前終止的RCT試驗WASIDtheWarfarin–AspirinSymptomaticIntracranialDiseaseSAMMPRISStentingandAggressiveMedicalManagementforPreventingRecurrentstrokeinIntracranialStenosisESASIStheEarlyStent-assistedAngioplastyinSymptomaticIntracranialStenosisRCT-NO.1NEnglJMed,2005;352(13):1305-1316.ComparisonofWarfarinandAspirin

forSymptomaticIntracranialArterialStenosisBackgroundAtheroscleroticintracranialarterialstenosisisanimportantcauseofstroke.Warfariniscommonlyusedinpreferencetoaspirinforthisdisorder,butthesetherapieshavenotbeencomparedinarandomizedtrial.RCT-NO.1TheWarfarin-AspirinSymptornaticIntracranialDiseaseStudy(NEUROLOGY1995;45:1488-1493.)151Patientswith50to99%stenosisofanintracranialarterywereidentifiedbyreviewingtheresultsofconsecutiveangiogramsperformedatparticipatingcentersbetween1985and1991.Figure.GraphshowsKaplan-Meierestimatesofproportionofpatientsremainingfreeofischemicstroke,myocardialinfarction,orsuddendeathinthosetreatedwithwarfarin(uppercurve)oraspirin(lowercurve).Therelativeriskofamajorvasculareventinthosetreatedwithwarfarinwas0.46(95%CI,0.23to0.86)comparedwithpatientstreatedwithaspirin.MethodsWerandomlyassignedpatientswithtransientischemicattackorstrokecausedbyangiographicallyverified50to99percentstenosisofamajorintracranialarterytoreceivewarfarin(targetinternationalnormalizedratio,2.0to3.0)oraspirin(1300mgperday)inadouble-blind,multicenterclinicaltrial.Theprimaryendpointwasischemicstroke,brainhemorrhage,ordeathfromvascularcausesotherthanstroke.RCT-NO.1After569patientshadundergonerandomization,enrollmentwasstoppedbecauseofconcernsaboutthesafetyofthepatientswhohadbeenassignedtoreceivewarfarin.ResultsRCT-NO.1ConclusionsWarfarinwasassociatedwithsignificantlyhigherratesofadverseeventsandprovidednobenefitoveraspirininthistrial.Aspirinshouldbeusedinpreferencetowarfarinforpatientswithintracranialarterialstenosis.RCT-NO.1StentingversusAggressiveMedicalTherapy

forIntracranialArterialStenosisNEnglJMed2011;365(11):993-1003.RCT-NO.2BackgroundAtheroscleroticintracranialarterialstenosisisanimportantcauseofstrokethatisincreasinglybeingtreatedwithpercutaneoustransluminalangioplastyandstenting(PTAS)topreventrecurrentstroke.However,PTAShasnotbeencomparedwithmedicalmanagementinarandomizedtrial.RCT-NO.2MethodsWerandomlyassignedpatientswhohadarecenttransientischemicattackorstrokeattributedtostenosisof70to99%ofthediameterofamajorintracranialarterytoaggressivemedicalmanagementaloneoraggressivemedicalmanagementplusPTASwiththeuseoftheWingspanstentsystem.Theprimaryendpointwasstrokeordeathwithin30daysafterenrollmentorafterarevascularizationprocedureforthequalifyinglesionduringthefollow-upperiodorstrokeintheterritoryofthequalifyingarterybeyond30days.RCT-NO.2此數據有問題Currently,themeandurationoffollowup,whichisongoing,is11.9months.ResultsRCT-NO.2ConclusionsInpatientswithintracranialarterialstenosis,aggressivemedicalmanagementwassuperiortoPTASwiththeuseoftheWingspanstentsystem,bothbecausetheriskofearlystrokeafterPTASwashighandbecausetheriskofstrokewithaggressivemedicaltherapyalonewaslowerthanexpected.

RCT-NO.2此數據有問題AggressivemedicalmanagementMedicalmanagementisidenticalinthetwogroupsandconsistsofaspirin,atadoseof325mgperday;clopidogrel,atadoseof75mgperdayfor90daysafterenrollment;managementoftheprimaryriskfactors(elevatedsystolicbloodpressureandelevatedlow-densitylipoprotein[LDL]cholesterollevels);andmanagementofsecondaryriskfactors(diabetes,elevatednon–high-densitylipoprotein[non-HDL]cholesterollevels,smoking,excessweight,andinsufficientexercise)withthehelpofalifestylemodificationprogram.RCT-NO.2AspirinplusclopidogrelMATCHCHARISMACUREAggressivemedicalmanagementWithrespecttotheprimaryriskfactors,wetargetedasystolicbloodpressureoflessthan140mmHg(<130mmHginthecaseofpatientswithdiabetes)andanLDLcholesterolleveloflessthan70mgperdeciliter(1.81mmolperliter).Weprovidetheaspirin,clopidogrel,onedrugfromeachmajorclassofantihypertensiveagents,rosuvastatin,andthelifestyleprogramtothestudypatients.RCT-NO.214.7%5.8%3.8%(35%relativeriskreduction)AcomparisonbetweentheSAMMPRISandESASIStrialsClinicalTrialRegistration:CUHK_CCT00116at.hkRCT-NO.3WiththeannouncementofthesafetyconcernandearlyterminationoftheSAMMPRIStrial,theDataSafetyMonitoringBoard(DSMB)ofESASISstudymetonApril28,2011andreviewedthe30-daysafetydata(combinedstrokeanddeath)for77patientsrandomizedasofApril20,2011.InhislettertotheExecutiveCommittee,theChairoftheDSMBcommentedthat‘…Thesafetydataforthemedicalgroupiscomparabletothe6%reportedforthemedicalarmoftheSAMMPRISstudy,whereasthesafetydataforthestentinggroupis