一級(jí)預(yù)防的抗栓：現(xiàn)狀與未來(lái)課件

AntithombosisinPrimary

PreventionWheredowestand/wherearewe

goingDr.CarlosBrotonsPrimary

prevention

trials

with

Aspirin:

review

of

the

Evidence1988 BritishDoctors'Trial1998 ThrombosisPreventionTrialHypertensionOptimalTreatment(HOT)Study1989 Physicians'HealthStudyPrimaryPreventionProject2005Women’sHealthStudyMeta-Analysis

ofDatafrom

the

Six

Primary

Prevention

Trials

ofCardiovascular

Events

Using

AspirinAlfredA.Bartolucci,PhD*,andGeorgeHoward,DrPHAmJCardiol2006;98:746Aspirinintheprimarypreventionofcardiovascular(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.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.ResultsoftheMeta-analysisregardingthepreventionofcoronaryheartdiseaseTheoverallriskreductionoftotalCHD(nonfatalandfatalMIanddeathduetoCHD)wasinfavorofaspirintherapy

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

(OR0.945;p=0.336)

ResultsoftheMeta-analysisregardingthepreventionofthestrokeBDTTPTHOTPPPCombinedWHSPHS0.5 1 2Oddsratioand95%CIFavoursaspirin FavoursplaceboAspirin

for

the

Primary

Prevention

ofCardiovascularEventsinWomen

and

MenASex-SpecificMeta-analysis

of

Randomized

Controlled

TrialsBergerJS.JAMA2006;30632%EffectofAspirinTreatmentonthePrimaryPreventionofMyocardialInfarction17%EffectofAspirinTreatmentonthePrimaryPreventionofStroke,IschemicStrokeandHemorrhagicStroke24%EffectofAspirinTreatmentonthePrimaryPreventionofIschemicStroke32%28%EffectofAspirinTreatmentonMajorBleedingAbsolute

risk

is

very

low:less

than1%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%±21.00.50.01.52.0ControlAntiplatelet

MI,myocardialinfarction

AntithromboticTrialists’Collaboration.BMJ.2002;324:71–86Reductioninseriousvasculareventswithantiplatelettherapyinhigh-riskpatients

287studies,135.000patients*Antithrombotic

Trialists’Collaboration.BMJ2002;324:7175-150mg

aspirin

daily

is

considered

routinely

for

all

such

patientsathigher

risk

ofvascularevents(morethan2%ayear)irrespective

of

whether

they

have

alreadyamajorvasculareventMajorCVeventsRelative

risk

reduction

vs

absolute

risk

reductionHIGHRISKPATIENTS*LOWRISKPATIENTS**RRR2215ARR25per1000treatedNNT403per1000treatedNNT333*Antithrombotic

Trialists’Collaboration.BMJ2002;324:71**Meta-analysis

ofRCT.JAMA2006;296MajorCVeventsRelative

risk

reduction

vs

absolute

risk

reductionALTHOUGHRELATIVEBENEFITSAPPEAREDBROADLYSIMILARINHIGHRISKANDLOWRISKPATIENTSTHEABSOLUTEBENEFITSINLOWRISKPATIENTSISVERYSMALL.*Antithrombotic

Trialists’Collaboration.BMJ2002;324:71**Meta-analysis

ofRCT.JAMA2006;296GuidelinessupporttheuseofaspirinforprimarypreventionofCVeventsEuropeanguidelinesonCVDpreventioninclinicalpractice(2007)AmericanHeartAssociation(AHA)/Evidence-basedAHAguidelines

forCVDpreventioninwomen(2007update).Theguidetoclinicalpreventiveservices2008:recommendationsoftheU.S.PreventiveServicesTaskForce(USPSTF).AmericanCollegeofChestPhysiciansE-BClinicalPracticeGuidelines-AntiplateletDrugs(2008)EuropeanguidelinesonCVDpreventioninclinicalpracticeAspirin(75mgdaily)canbeconsideredinallpatientswithCVD,andinthoseathighriskofdevelopingCVD(SCORE>10%over10years)oncebloodpressurehasbeencontrolled(ascloselyaspossibletothegoaloflessthan140/90mmHg)InlowerriskindividualsasmallabsolutevascularbenefitbyaspirinmaybeoffsetbytheslightlygreaterabsoluteriskofbleedingcomplicationsEJCPR2007;vol14(suppl2):S1-S113AmericanHeartAssociation(AHA)GuidelinesBenefits

of

reducingCVrisk

outweigh

these

risksinmost

patients

with

higher

coronary

risk

Doses

of

aspirin75–160mg

per

dayareaseffectiveashigher

doses

Consider

aspirin75–160mg

per

day

for

peopleathigher

risk(especially

those

witha10-yearCHDrisk

of10percent

or

greater)Circulation2002;106:338-391AHAguidelines

forCVDpreventioninwomen(2007update)Aspirin:high-riskAnyvasculardisease,end-stageorchronicrenaldisease,diabetesmellitus,and10-yearFraminghamrisk>20%Aspirintherapy75to325mgperdayshouldbeusedinhigh-riskwomenunlesscontraindicated(ClassI,LevelA)Circulation2007;115:1481-1501Guidetoclinicalpreventiveservices2008:recommendationsfromUSPSTFUSPSTFstrongly

recommends

that

clinicians

discussaspirinchemoprevention

withadultswho

areatincreased

riskforCHDDiscussionswith

patients

shouldaddressboth

the

potential

benefitsandharmsofaspirintherapy

Grade:ARecommendationGuidetoclinicalpreventiveservices2008:recommendationsfromUSPSTFBaselineriskforCHDover5years:1%Totalmortality:noeffectCHDevents:1?4avoidedHemorrhagicstrokes:0?2causedMajorgastrointestinalbleedingevents:2?4causedGuidetoclinicalpreventiveservices2008:recommendationsfromUSPSTFBaselineriskforCHDover5years:3%Totalmortality:noeffectCHDevents:4?12avoidedHemorrhagicstrokes:0?2causedMajorgastrointestinalbleedingevents:2?4causedGuidetoclinicalpreventiveservices2008:recommendationsfromUSPSTFBaselineriskforCHDover5years:5%Totalmortality:noeffectCHDevents:6?20avoidedHemorrhagicstrokes:0?2causedMajorgastrointestinalbleedingevents:2?4causedWhoshouldbetreatedwithaspirin?The

decisiontouseaspirinshouldbebasedonabalanceofthe

risksandbenefitsforeach

person

taking

into

account

their

absolute

riskforCHDorCVD.Patients

with

establishedCVDorvery

high

risk

patients

shouldbetreated

withaspirinunless

contraindicated.BeforestartingtreatmentwithaspirinalwaysconsiderrisksfactorsforGIbleedingsuchasageandconcomitantuseofNSAIDS.AnunansweredquestionIn

primary

prevention

iswhetherthebenefitsofdailyaspirinoutweightstheharmsinspecific

populations(suchasthose

with

moderate

riskofCHD)AntithombosisinPrimary

Prevention

Wherearewe

going?

Ongoingtrialstoassessthebenefit:riskprofileoflow-doseaspirininthepreventionof

firstCVeventsTheARRIVEStudy

(AspirintoReduceRiskofInitialVascularEvents)

RationaleARRIVEwillexpandthealreadyexisting,strongbodyofevidencesupportingaspirinforprimarypreventionofCVDeventsARRIVEwasdesignedtodemonstratetheefficacyandsafetyoflow-doseaspirininamoderate-riskpopulationCHDriskcontinuumARRIVE#ofMIsprevented(Per1,000patientstreated

for10years)CHD10-yearRiskBENEFIT>RISKBENEFIT>>RISKBENEFIT>>>>RISKOverallCHD,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%OverviewoftheARRIVETrialSampleSize:12,000patients(6,000pergroup)willbeenrolledDurationofStudy:approximately5yearsStudyLocations:Morethan400trialsitesac