一级预防的抗栓现状与未来

一级预防的抗栓现状与未来第1页/共36页PrimarypreventiontrialswithAspirin:reviewoftheEvidence1988 BritishDoctors'Trial1998 ThrombosisPreventionTrialHypertensionOptimalTreatment(HOT)Study1989 Physicians'HealthStudyPrimaryPreventionProject2005Women’sHealthStudy第2页/共36页Meta-AnalysisofDatafromtheSixPrimaryPreventionTrialsofCardiovascular

EventsUsingAspirinAlfredA.Bartolucci,PhD*,andGeorgeHoward,DrPHAmJCardiol2006;98:746第3页/共36页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页/共36页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页/共36页ResultsoftheMeta-analysisregardingthepreventionofcoronaryheartdiseaseTheoverallriskreductionoftotalCHD(nonfatalandfatalMIanddeathduetoCHD)wasinfavorofaspirintherapy

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

(OR0.945;p=0.336)

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

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

Wherearewegoing?

Ongoingtrialstoassessthebenefit:riskprofileoflow-doseaspirininthepreventionof

firstCVevents第26页/共36页TheARRIVEStudy

(AspirintoReduceRiskofInitialVascularEvents)第27页/共36页

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

for10years)CHD10-yearRiskBENEFIT>RISKBENEFIT>>RISKBENEFIT>>>>RISK第29页/共36页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页/共36页OverviewoftheARRIVETrialSampleSize:12,000patients(6,000pergroup)willbeenrolledDurationofStudy:approximately5yearsStudyLocations:Morethan400trialsitesacrossGermany,Ireland,Italy,Poland,Spain,UK,USAGenderDistribution:70%male/30%femaleI