高脂血症的一级预防和二级预防课件

PrimaryandSecondaryPreventionofDyslipidemia:EstablishedTherapiesandEmergingParadigms

SidneyC.Smith,Jr.MDProfessorofMedicineDirector,CenterforCardiovascularScienceandMedicineUniversityofNorthCarolinaatChapelHillMostMIsAriseFromSmaller,

Nonflow-limitingStenoses68%18%14%020406080<50%50%–70%>70%%StenosisPercentofMIPatientsAdaptedfromFalketal.Circulation1995;92:657–671.PCICABGEffectsofStatinsonCoronaryDisease:Primary&SecondaryPreventionStudy

LDL

LDL

Rx

RRR

ARR

NNT4S188122(-35%)34%*8.5%12CARE13998(-32%)24%*3.0%34LIPID150113(-25%)23%*3.4%30WSCPS192159(-26%)29%*2.2%46AFCAPS150113(-25%)36%^1.8%56*=NFMI/CHDmort.^=NF/FMI,UAP

%**†‡§*Confidenceinterval(CI)notreported.†95%CI,14%-41%.‡95%CI,16%-37%.§95%CI,12%-31%.HebertPRetal.JAMA.1997;278:313-321.ImpactofLoweringLDL-ConCVDEventsandTotalMortalityNonfatal/

fatalCHDCVD

mortality4S: MajorCHDEventReductioninaSubgroupofPatientsWithDiabetesPyöräläKetal.DiabetesCare.1997;20:614-620.Proportion

without

majorCHDeventYrsincerandomization-P=0.002-P=0.0001Diabetic,simvastatinDiabetic,placeboNondiabetic,simvastatinNondiabetic,placebo32%55%4S:TreatmentBenefitinSubgroupWith

ImpairedFastingGlucose(FG110-125mg/dL)HaffnerSMetal.Diabetes.1998;(suppl1):A54.Abstract.Total

mortalityCoronary

mortalityMajor

coronary

eventsRevas-

culari-

zationsin

events

(%)P=0.005P=0.001P=0.010ClinicalTrialFindings:TheStatinsStatinsLDL-Cby25%-35%BenefitsatvariousLDL-Clevels;evidentsoonaftertherapy

inLDL-CrequiredforinCHDmorbidity/mortality

inall-causemortalityin2°preventionandincardiovascularmortalityin1°preventionStudiessupporttreatmentinvariouspatientgroupswomenelderlydiabeticsLipidLoweringTherapyforthePreventionofVascularDisease

WhenShouldLipidLoweringTherapybestarted?WhatshouldbetheTreatmentGoal?FindingsoftheHPSStudy.ShouldHDL–CholesterolbeaTarget?WhentoStartCholesterolLoweringTherapyinPatientswithCoronaryHeartDisease“Thecardiovascularspecialistorattendingphysicianshouldberesponsibleforstartingsomeformofcholesterolloweringtherapyinpatientsupondischargefromthehospitalafteracutecoronaryevents……….Thecardiovascularspecialistthusshouldinsurethatappropriatetherapyisinitiatedandmaintained.”AHAScienceAdvisoryCirc.1997;95:1683MIRACL

ACS:ATreatmentGapAcutecoronaryevent4S3AFCAPS/TexCAPS/

WOSCOPSCARE1LIPID2NohistoryofCADAcuteCoronarySyndromes3mot=06moRandomization:

CARE-3–20mo

LIPID-3–36moRandomization:

>6moStableCADPrimarypreventionSecondarypreventionDurationoffollow-up:15.0years;26.1years;35.4years.SchwartzGGetal.AmJCardiol1998;81:578–581.TimeofHighMortality71249-27-405-16-50-40-30-20-1001020TCLDL-CHDL-CTGPlaceboAtorvastatin80mg%MIRACL:ChangeinLipidLevelsDatafromSchwartzGGetal.JAMA.2001;285:1711-1718.

AdditionaldatacourtesyofGGSchwartz.unstableangina

ornon–Q-waveMI3,086randomized24–96hafteradmissionFollowed16weeks0510150481216Timesincerandomization(wk)Cumulative

incidence

(%)RR=0.84

(95%CI,0.70-1.00)

P=0.048AtorvastatinPlacebo17.414.8*Death(anycause),nonfatalMI,resuscitatedcardiacarrest,recurrentsymptomatic

myocardialischemiawithobjectiveevidencerequiringemergencyrehospitalization.

SchwartzGGetal.JAMA.2001;285:1711-1718.MIRACL:TimetoFirstIschemicEvent*MIRACL:OccurrenceofPrimaryCombinedEndPoint0.250.500.751.001.252.00AtorvastatinbetterPlacebobetterRelativeriskDeathNonfatalMIResuscitatedcardiacarrestRecurrentsymptomaticmyocardialischemia

withobjectiveevidencerequiringemergencyrehospitalizationNo.(%)ofeventsAtorva

Placebo64(4.2)

68(4.4)101(6.6)

113(7.3)8(0.5)

10(0.6)95(6.2)

130(8.4)**P=0.02AdaptedfromSchwartzGGetal.JAMA.2001;285:1711-1718.0.00.51.01.52.00481216Timesincerandomization(wk)RR=0.50

(95%CI,0.26-0.99)P=0.045AtorvastatinPlacebo1.60.8MIRACL:FatalorNonfatalStrokeCumulative

incidence

(%)DatafromSchwartzGGetal.JAMA.2001;285:1711-1718.19,599menandwomen<80yodischargedpostAMI,58SwedishHospitals,1995-19985528(28%)statinrxvs14071(72%)nostatinrx,highesthospitalratesofuse48%;lowest12%StenestrandJAMA2001;285;430-436EarlyStatinTreatmentandSurvivalinAMIRR0.75(0.63-0.89)P=0.001

25%RiskReductionPRISM:EventRateCur

vesHeeschenCetal.Circulation.2002;105:1446-1452. 0 5 10 15 20 25 30181614121086420Follow-up(day)Eventrates

(%)StatinsdiscontinuedNostatinsStatinscontinuedEvents=mortality,MIStatinTrialsandGoalsof

Cholesterol-LoweringTherapyGrundy.Circulation.1998;97:1436-1439.ThequantitativerelationbetweenthemagnitudeofcholesterolloweringandCHDreductionhasnotbeenpreciselydefined3modelsa)Linearb)Thresholdc)Curvilinear2520151050507090110130150170190210TNT80mgTNT10mgCARE-SLIPID-S4S-SCARE-PLIPID-PTNTEntry4S-PCHDEvent(%)LDL-C(mg/dL)CorrelationBetweenCHDEvents

andLDL-CLevelsS=Statintreated;P=PlacebotreatedAVERT80mg:

LDL=77mg/dL13.4%EventRateIIIaIIbIIII-InterventionisusefulandeffectiveIIa-Weightofevidence/opinionisinfavorofusefulness/efficacyIIb-Usefulness/efficacyislesswellestablishedbyevidence/opinionIII-Interventionisnotuseful/effectiveandmaybeharmfulDatafrommanylarge,RCTsDatafromfewer,smallerRCTS,carefulanalysesofnonrandomizedstudies,observationalregistriesExpertconsensus=Levelof

evidenceClassificationofRecommendationsACC/AHAPracticeGuidelinesLIPIDLOWERINGAT

HOSPITALDISCHARGELipid-loweringagentanddietinpatientswithLDLcholesterol>130mg/dL

Lipid-loweringagentifLDLcholesterollevelis>100mg/dLIIbAAIACC/

AHAUA/NSTEMIGuidelines2002MRC/BHFHeartProtectionStudy:ELIGIBILITYIncreasedriskofCHDdeathduetopriordisease: -Myocardialinfarctionorothercoronaryheartdisease -Occlusivediseaseofnon-coronaryarteries -Diabetesmellitus,TypeIorII -TreatedHypertensionAge40-80years20,536participants(men=15,454,women=5,082)

Totalcholesterol>3.5mmol/l(>135mg/dl)Statinorvitaminsnotconsideredclearlyindicatedorcontraindicatedbypatient’sowndoctorsHEARTPROTECTIONSTUDY(HPS)MAJORVASCULAREVENTSRiskratioand95%CISTATINPLACEBOVascularevent(10269)(10267)STATINbetterSTATINworseTotalCHD9141234Totalstroke456613Revascularization9261185ANYOFABOVE20422606(19.9%)(25.4%)24%SE2.6reduction(2P<0.00001)1.01.21.4HEARTPROTECTIONSTUDY(HPS)

VASCULAREVENTbyPRIORDISEASERiskratioand95%CISTATINPLACEBOBaselinefeature(10269)(10267)STATINbetterSTATINworseSTATINworsePreviousMI10071255OtherCHD(notMI)452597NopriorCHD

CVD182215PVD332427Diabetes279369ALLPATIENTS20422606(19.9%)(25.4%)24%SE2.6reduction(2P<0.00001)1.01.21.4HEARTPROTECTIONSTUDY(HPS)

:VASCULAREVENTbyLDLRiskratioand95%CISTATINPLACEBOBaselinefeature(10269)(10267)STATINbetterSTATINworseLDL(mg/dl)Hetc22=0.8<100285360100<130670881LLPATIENTS20422606(19.9%)(25.4%)24%SE2.6reduction(2P<0.00001)1.01.21.4(2.6mmol/l)(3.4mmol/l)HPS:EffectsofSimvastatinonVascularEventsbyYear01020300123456Proportionwith

event(%)Yearsoffollow-upBenefit/1,000(SE) 5(3) 20(4) 35(5) 46(5) 54(7) 60(18)Logrank

P

<0.0001PlaceboSimvastatin®©2002ThomsonProfessionalPostgraduateServices®HPSCollaborativeGroup.Lancet.2002;360:7-22.HPS:AbsoluteRiskReductionsEventPlaceboAbsoluteRiskSimvastatinAbsoluteRiskARRNNTMajorVascular25.2%(2,585/10,267)19.8%(2,033/10,269)5.4%18All-CauseDeath14.7%(1,507/10,267)12.9%(1,328/10,269)1.8%56Stroke5.7%

(585/10,267)4.3%

(444/10,269)1.4%71ARR=absoluteriskreduction;NNT=numberneededtotreat.®©2002ThomsonProfessionalPostgraduateServices®HPSCollaborativeGroup.Lancet.2002;360:7-22.HPSenrolledhigh-riskprimary-andsecondary-preventionpatients.HPS.Lancet.2002;360:7.Downs.JAMA.1998;279:1615.LIPID.NEnglJMed.1998;339:1349.Sacks.NEnglJMed.1996;335:1001.4S.Lancet.1995;345:1274.Shepherd.NEnglJMed.1995;333:1301.

RelationBetweenCHDEventsandLDL-COutcomesinStatinTrials%withCHDeventMeanLDL-Clevelatfollow-up(mg/dL)05101520253090110130150170190210CARE-RxLIPID-Rx4S-RxCARE-PILIPID-PI4S-PI2°Prevention1°PreventionWOSCOPS-PIWOSCOPS-RxAFCAPS-RxAFCAPS-PIHPS-PlHPS-RxHPS-RxHPS-Plw/revasc+

strokeCHDonlyPI=placeboRx=treatment70®©2002ThomsonProfessionalPostgraduateServices®AFCAPS/TexCAPS:LovastatininPrimaryPrevention—RiskReductionsAcrossBaselineHDL-CTertilesDownsJR,etal.JAMA.1998;279:1615.012345678LovastatinPlacebo344035–39HDL-CTertile(mg/dL)Events,%

VAHIT:FavorableEffectsofFibrateonCVDEventsinCHDPatientsWithIsolatedLowHDL-C*P<0.01;†P=0.006;‡P=0.05

P=placebogroup;Rx=treatedgroup.PresentedbyHBRubinsatthe71stannual

AHAScientificSessions;Dallas,Texas.Subjects:2,531menAge:£74(avg64)yrMeanbaselineLDL-C:111mg/dLMeanbaselineHDL-C:32mg/dLMeanbaselineTG:161mg/dLDuration:7yrIntervention:Gemfibrozil

600mgbid%+P/Rx 111/115 32/34 161/122 274/219 118/93 88/64 219/197**†‡LDL-CHDL-CTGNonfatal

MI/CHD

deathCHD

deathAll-cause

mortalityStrokeHATS:ClinicalEndpointsBrownBG,etal.NEnglJMed.2001;345:1521.414.30510152025CoronaryDeath,MI,Stroke,orRevascularizationCompositeEventRate,%89%

Reduction**P<.05