一級預(yù)防的抗栓現(xiàn)狀與未來

一級預(yù)防的抗栓現(xiàn)狀與未來第1頁/共36頁PrimarypreventiontrialswithAspirin:reviewoftheEvidence1988 BritishDoctors'Trial1998 ThrombosisPreventionTrialHypertensionOptimalTreatment(HOT)Study1989 Physicians'HealthStudyPrimaryPreventionProject2005Women’sHealthStudy第2頁/共36頁Meta-AnalysisofDatafromtheSixPrimaryPreventionTrialsofCardiovascular

EventsUsingAspirinAlfredA.Bartolucci,PhD*,andGeorgeHoward,DrPHAmJCardiol2006;98:746第3頁/共36頁Aspirinintheprimarypreventionofcardiovascular(CV)eventsTrialPatientpopulationAgerange(years)Aspirin

dosageBDT(1988)1Apparentlyhealthymalephysicians(n=5,139)50–78500mg/dayPHS(1989)2Apparentlyhealthymalephysicians(n=22,071)40–84325mgqodHOTstudy(1998)3MenandwomenwithDBP100–115mmHg(n=18,790)50–8075mg/dayTPT(1998)4Menathighriskofheartdisease(n=5,499)45–6975mg/dayPPP(2001)5Menandwomenwith1majorCVriskfactor(n=4,495)50–80+100mg/dayWHS(2005)6Apparentlyhealthywomen(n=39,876)45100mgqodBDT,BritishDoctors’Trial;HOT,HypertensionOptimalTreatment;PHS,Physicians’HealthStudy;PPP,PrimaryPreventionProject;qod,everyotherday;TPT,ThrombosisPreventionTrial;WHS,Women’sHealthStudy.1.PetoR,etal.BMJ1988;296:313–6;2.PhysiciansHealthStudy.NEnglJMed1989;321:1825–8;3.HanssonL,etal.

Lancet1998;351:1755–62.4.TheMedicalResearchCouncil’sGeneralPracticeResearchFramework.Lancet1998;351:

233–41;5.deGaetanoG,etal.Lancet2001;357:89–95.6.RidkerPM,etal.NEnglJMed2005;352:1293–304.第4頁/共36頁Primaryfindings(totalCVevents)fromthesixkeytrialsStudyNameRiskAspirinControl/PlaceboOddsBDTLow260/3429127/17101.0230.842PHSLow292/11037390/110340.7690.001TPTHigh208/1268250/12720.7410.003HOTLow243/9399290/93910.8240.033PPPLow46/222665/22690.5460.006WHSLow539/19934585/199420.9820.780TOTAL1588/472931707/456180.869<0.0001OddsRatioand95%CI0.512ASPIRINCONTROL/PLACEBOPetoR,etal.BMJ1988;296:313–6;Physicians’HealthStudy.NEnglJMed1989;321:1825–8;MansonJE,etal.JAMA1991;266:521–7;HanssonL,etal.Lancet1998;351:1755–62.TheMedicalResearchCouncil’sGeneralPracticeResearchFramework.Lancet1998;351:233–41;deGaetanoG.Lancet2001;357:89–95.RidkerPM,etal.NEnglJMed2005;352:1293–304.第5頁/共36頁ResultsoftheMeta-analysisregardingthepreventionofcoronaryheartdiseaseTheoverallriskreductionoftotalCHD(nonfatalandfatalMIanddeathduetoCHD)wasinfavorofaspirintherapy

(oddsratioof0.77)BDTPHSHOTPPPWHSCombinedTPT0.5 1 2Favoursaspirin FavoursplaceboOddsratioand95%CICHD,coronaryheartdiseaseBartolucciAA,etal.AmJCardiol2006;98:746–50..第6頁/共36頁BartolucciAA,etal.AmJCardiol2006;98:746–50.Meta-analysisofsixprimarypreventiontrialsshowednodifferencesforthepreventionofstroke

(OR0.945;p=0.336)

ResultsoftheMeta-analysisregardingthepreventionofthestrokeBDTTPTHOTPPPCombinedWHSPHS0.5 1 2Oddsratioand95%CIFavoursaspirin Favoursplacebo第7頁/共36頁AspirinforthePrimaryPreventionofCardiovascularEventsinWomenandMenASex-SpecificMeta-analysisofRandomizedControlledTrialsBergerJS.JAMA2006;306第8頁/共36頁32%EffectofAspirinTreatmentonthePrimaryPreventionofMyocardialInfarction第9頁/共36頁17%EffectofAspirinTreatmentonthePrimaryPreventionofStroke,IschemicStrokeandHemorrhagicStroke第10頁/共36頁24%EffectofAspirinTreatmentonthePrimaryPreventionofIschemicStroke第11頁/共36頁32%28%EffectofAspirinTreatmentonMajorBleedingAbsoluteriskisverylow:lessthan1%第12頁/共36頁Reductioninseriousvasculareventswithantiplatelettherapyinhigh-riskpatients

287studies,135.000patientsCategory

%oddsreductionAcuteMI Acutestroke PriorMI Priorstroke/transientischemicattack Otherhighrisk:Coronaryarterydisease

(e.g.,unstableangina,heartfailure) Peripheralarterialdisease

(e.g.,intermittentclaudication) Highriskofembolism(e.g.,atrialfibrillation) Other(e.g.,diabetesmellitus) Alltrials22%±21.00.50.01.52.0ControlAntiplateletMI,myocardialinfarction

AntithromboticTrialists’Collaboration.BMJ.2002;324:71–86第13頁/共36頁Reductioninseriousvasculareventswithantiplatelettherapyinhigh-riskpatients

287studies,135.000patients*AntithromboticTrialists’Collaboration.BMJ2002;324:7175-150mgaspirindailyisconsideredroutinelyforallsuchpatientsathigherriskofvascularevents(morethan2%ayear)irrespectiveofwhethertheyhavealreadyamajorvascularevent第14頁/共36頁MajorCVeventsRelativeriskreductionvsabsoluteriskreductionHIGHRISKPATIENTS*LOWRISKPATIENTS**RRR2215ARR25per1000treatedNNT403per1000treatedNNT333*AntithromboticTrialists’Collaboration.BMJ2002;324:71**Meta-analysisofRCT.JAMA2006;296第15頁/共36頁MajorCVeventsRelativeriskreductionvsabsoluteriskreductionALTHOUGHRELATIVEBENEFITSAPPEAREDBROADLYSIMILARINHIGHRISKANDLOWRISKPATIENTSTHEABSOLUTEBENEFITSINLOWRISKPATIENTSISVERYSMALL.*AntithromboticTrialists’Collaboration.BMJ2002;324:71**Meta-analysisofRCT.JAMA2006;296第16頁/共36頁GuidelinessupporttheuseofaspirinforprimarypreventionofCVeventsEuropeanguidelinesonCVDpreventioninclinicalpractice(2007)AmericanHeartAssociation(AHA)/Evidence-basedAHAguidelinesforCVDpreventioninwomen(2007update).Theguidetoclinicalpreventiveservices2008:recommendationsoftheU.S.PreventiveServicesTaskForce(USPSTF).AmericanCollegeofChestPhysiciansE-BClinicalPracticeGuidelines-AntiplateletDrugs(2008)第17頁/共36頁EuropeanguidelinesonCVDpreventioninclinicalpracticeAspirin(75mgdaily)canbeconsideredinallpatientswithCVD,andinthoseathighriskofdevelopingCVD(SCORE>10%over10years)oncebloodpressurehasbeencontrolled(ascloselyaspossibletothegoaloflessthan140/90mmHg)InlowerriskindividualsasmallabsolutevascularbenefitbyaspirinmaybeoffsetbytheslightlygreaterabsoluteriskofbleedingcomplicationsEJCPR2007;vol14(suppl2):S1-S113第18頁/共36頁AmericanHeartAssociation(AHA)GuidelinesBenefitsofreducingCVriskoutweightheserisksinmostpatientswithhighercoronaryriskDosesofaspirin75–160mgperdayareaseffectiveashigherdosesConsideraspirin75–160mgperdayforpeopleathigherrisk(especiallythosewitha10-yearCHDriskof10percentorgreater)Circulation2002;106:338-391第19頁/共36頁AHAguidelinesforCVDpreventioninwomen(2007update)Aspirin:high-riskAnyvasculardisease,end-stageorchronicrenaldisease,diabetesmellitus,and10-yearFraminghamrisk>20%Aspirintherapy75to325mgperdayshouldbeusedinhigh-riskwomenunlesscontraindicated(ClassI,LevelA)Circulation2007;115:1481-1501第20頁/共36頁Guidetoclinicalpreventiveservices2008:recommendationsfromUSPSTFUSPSTFstronglyrecommendsthatcliniciansdiscussaspirinchemopreventionwithadultswhoareatincreasedriskforCHDDiscussionswithpatientsshouldaddressboththepotentialbenefitsandharmsofaspirintherapyGrade:ARecommendation第21頁/共36頁Guidetoclinicalpreventiveservices2008:recommendationsfromUSPSTFBaselineriskforCHDover5years:1%Totalmortality:noeffectCHDevents:1?4avoidedHemorrhagicstrokes:0?2causedMajorgastrointestinalbleedingevents:2?4caused第22頁/共36頁Guidetoclinicalpreventiveservices2008:recommendationsfromUSPSTFBaselineriskforCHDover5years:3%Totalmortality:noeffectCHDevents:4?12avoidedHemorrhagicstrokes:0?2causedMajorgastrointestinalbleedingevents:2?4caused第23頁/共36頁Guidetoclinicalpreventiveservices2008:recommendationsfromUSPSTFBaselineriskforCHDover5years:5%Totalmortality:noeffectCHDevents:6?20avoidedHemorrhagicstrokes:0?2causedMajorgastrointestinalbleedingevents:2?4caused第24頁/共36頁Whoshouldbetreatedwithaspirin?ThedecisiontouseaspirinshouldbebasedonabalanceoftherisksandbenefitsforeachpersontakingintoaccounttheirabsoluteriskforCHDorCVD.PatientswithestablishedCVDorveryhighriskpatientsshouldbetreatedwithaspirinunlesscontraindicated.BeforestartingtreatmentwithaspirinalwaysconsiderrisksfactorsforGIbleedingsuchasageandconcomitantuseofNSAIDS.AnunansweredquestionInprimarypreventioniswhetherthebenefitsofdailyaspirinoutweightstheharmsinspecificpopulations(suchasthosewithmoderateriskofCHD)第25頁/共36頁AntithombosisinPrimaryPrevention

Wherearewegoing?

Ongoingtrialstoassessthebenefit:riskprofileoflow-doseaspirininthepreventionof

firstCVevents第26頁/共36頁TheARRIVEStudy

(AspirintoReduceRiskofInitialVascularEvents)第27頁/共36頁

RationaleARRIVEwillexpandthealreadyexisting,strongbodyofevidencesupportingaspirinforprimarypreventionofCVDeventsARRIVEwasdesignedtodemonstratetheefficacyandsafetyoflow-doseaspirininamoderate-riskpopulation第28頁/共36頁CHDriskcontinuumARRIVE#ofMIsprevented(Per1,000patientstreated

for10years)CHD10-yearRiskBENEFIT>RISKBENEFIT>>RISKBENEFIT>>>>RISK第29頁/共36頁OverallCHD,Stroke,andCVDeath

Mean10-YearRisk(%)CHD(PROCAMandFramingham)STROKE(Framingham)CVDeath(SCORE)Total(CVD)High-riskcountries15.8%9.1%5.1%30.0%RiskEstimatesbyAgeandGender(AllCountries)Low-risk

countries8.5%9.1%2.75%20.3%Overall12.9%9.1%4.1%26.1%第30頁/共36頁OverviewoftheARRIVETrialSampleSize:12,000patients(6,000pergroup)willbeenrolledDurationofStudy:approximately5yearsStudyLocations:Morethan400trialsitesacrossGermany,Ireland,Italy,Poland,Spain,UK,USAGenderDistribution:70%male/30%femaleI