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现代脂质三联治疗IntroductionPartIEfficacy-ThePowertoReachTargetKeyFactor:+Differentiators:LDLReductionTGHDLLDL/HDLRa

tioTheLipidTriadTheLDL/HDLRatio-OurStrength,OurStory!!ClearpositioningforLipobayAnewperceptionofeffica

cyDifferentiationtoAtorvastatinFitwithourproductprofileLDLHDLAdditionalriskfactor,especiallyindiabeticsTheLipidTria

d-OverviewTGTheLipidTriadTheRatioTheLipidTriadandStrategicRationalePartII•Noscientificevidence•Evidencecontradicti

ngthisstatement•AmarketinghypothesistobuildtheirLDLstory•Creatingtheperceptionofthestatinwiththestrongesteff

icacyIt’slogicalIt’smeasurableIt’spracticableTheLipidTriad-TheGP’sPerspectiveSupportingDatafromLandmarkStudiesPartIII121086420%

MortalityPlaceboQ1Q2Q3Q4(lowHDL-increase)(highHDL-increase)4S-StudyCADMortalityperQuartilesofIncreasesinHDL-CholesterolKJEKSHUSJ&

PEDERSENT(unpublished)HDLInterventionTrial(VA-HIT)RUBINSHBetal.NewEnglJMed1999;341:41006-31-4-35-30-25-20-15-10-50510Cholestero

lLDL-CHDL-CTriglyceridesPercentchangecomparedtoplaceboat1yearSecondaryPreventionin2531menwithlowHDL-C&LD

L-Cshoweda22%reductionincombinedfatalandnon-fatalMIHDL-CholesterolasRiskFactorforCHDLRC-CPPT(Placebo)MRFIT(u

sualcare)IncidencerateofCHDIncidencerateofCHD121086420100130160190GORDONDJetal.Circulation1989;79:8-15.HDL-C[mg/dl]65554535LDL-

Cholesterolmg/dlLDL-Cholesterolmg/dl12108642010013016019000.511.522.53FraminghamHeartStudyCADriskasafunctiono

fLDL-CandHDL-Cinmen(50to70y)CASTELLIWP.AmJCardiol1998;82:60-6522016010085654525LDLCholesterol(mg/dL)024681

0121416LDL<=5LDL>5HDL>=1.08HDL<1.08LDL/HDL<=5LDL/HDL>5Incidenceofcardiacevents(per1000person-years)Gemfibr

ozilPlaceboLDL-CTertiles(mmol/L)HDL-CTertiles(mmol/L)LDL-C/HDL-CTertiles244632363445223938531829Incidenceforcardiaceventsvslipidpa

rameterHelsinkiHeartStudyMANNINENV,LeenaT,KoskinenPetal.Circulation1992;85:37-45AFCAPS/TEXCAPSApoB/A1Tert

ilesLDL-C/HDL-CTertiles1.61.41.210.80.60.40.201.61.41.210.80.60.40.20EventRateper100Patient-YearsofRiskEventRateper100Patien

t-YearsofRisk0.88890.8898-1.02051.02523.77423.7744-4.4096.4101GOTTOAetal.Circulation2000;101:477-484

LDL/HDLRatioasTherapeuticSuccessPlaceboStatin2411631245050100150200250300<=5>5LDL/HDL-RatioTriglycerides<200mg/dlTrigl

ycerides>=200mg/dlCADcasesper1,000subjectsin6yearsASSMANNGandSCHULTEH;AmJCardiol1992;70:733-737IncidenceofCADvsLDL/HDLratiobyTGlevel(n=4559)PROCAMHea

rtStudy050100150200250300<3<4<5>5>6>7LDL/HDLratioCHDIncidence/1000in6yearsCHDriskaccordingtoLDL/HDLratioatbaselineASSMANNG;LipidMetabol

ismDisordersandCHD;MMVMedizinVerlag,1993:43PROCAMHeartStudyMeanvaluesfordevelopingatheroscleroticCHDwithin6yearsVariableCHDDevelopmentN

oCHDDevelopment(n=186)(n=4221)TC(mg/dl)251.8222.9HDL-C(mg/dl)39.545.2LDL-C(mg/dl)176.2147.1LDL/HDLratio4.723.4TG

(mg/dl)163.0134.5ASSMANNG;LipidMetabolismDisordersandCHD;MMVMedizinVerlag,1993:41PROCAMHeartStudyPredictivevalue

ofriskfactorsfordevelopingatheroscleroticCHDwithin6yearsVariableRiskRatioPredictivePower%TG200mg/dl2.37.5TC250(mg/dl)2.88.3LDL-C195(mg/dl)3.

712.0LDL-C155(mg/dl)3.37.1HDL-C35(mg/dl)3.911.0LDL/HDLratio56.416.5ASSMANNG;LipidMetabolismDisordersandCHD;MMVMedizinVerlag,1993:43PROCAMH

eartStudyHDLasCHDriskfactorshowed186events,inmenaged40-60years(n=4407)CHDIncidenceper1,000in6years020406080100120140

1603535-5555HDL-C(mg/dL)1103021ASSMANNG;LipidMetabolismDisordersandCHD;MMVMedizinVerlag,1993:59PROCAMHeartStudyLDLasC

HDriskfactorshowed177eventsinmenaged40-60years,(n=4263)CHDIncidenceper1,000in6years020406080100120140135135-154155-195195LDL-C(mg/dL)54

301631120ASSMANNG;LipidMetabolismDisordersandCHD;MMVMedizinVerlag,1993:60PROCAMHeartStudyExpertOpinion

sPartIVTheLipidTriad-ExpertCommentsAHA,November1999“EvaluatingtheriskonthebasesofLDLalone,isnaive”ValentinFuster,MountS

inaiMedicalCenter,NewYork“TheLDL/HDLratioisamuchstrongerpredictorfortheCHDriskthanLDLalone”PaulRidker,BrighamInstituteforWomen’sHospita

l,BostonACCP,March2000“LowHDLisabetterindicatorofCHDthanhighLDLasseeninepidemiologicalstudiessuchastheFraminghamStudyandrecentlytheVA-HITS

tudy.”SanderRobins,UniversityMedicalCenter,Boston“LandmarkstatintrialshaveshownconsistentbenefitsonCHDreductionafterraisingHDLby5-10%i

rrespectiveofLDLlevels”ChristieBallantyne,BaylorCollegeofMedicine,HoustonTheLipidTriad-ExpertCommentsHelsinkiHeartStudy“TheLDL/HDLratiowasthebes

tsinglepredictorofcardiacevents”ManninenV,LeenaT,KoskinenPetal.Circulation1992;85,1:37“Patientsintheplacebogroupwithtriglyceri

delevelsof200mg/dlandanLDL/HDLratioof5.0hadbyfarthehighestincidenceofcardiacevents”GerdAssmann,LipidMetabolismDisordersandCoronary

HeartDisease,MMVMedizinVerlag,1993TheLipidTriad-ExpertCommentsPROCAM“Thegreatestdifference,inrelativeterms,betw

eenthegroupswithandwithoutmajorcoronaryeventswasseenintheLDL/HDL-ratio”AssmannG,CullenPandSchulteH;EurHeartJournal1998,19A2-A11“F

orpracticalpurposesitappearsadvisabletobasepredictionsforatheroscleroticCADandtreatmentdecisiononafulllipidprofile

,(cholesterol,triglycerides,LDLandHDLcholesterol)ratherthancholesterolorLDLcholesteroldeterminantsalone”GerdAssmann,LipidMetabolismDisordersandCoron

aryHeartDisease,MMVMedizinVerlag,1993TheLipidTriad-ExpertCommentsStateoftheArtConference,BerlinApril2000“TheLipidTriadshouldformthebasesofd

iagnosticandtherapeuticdecisionsinlipidtherapy”MarkolfHanefeld,InstituteforMetabolismDisordersandResearc

h,Dresden“ByjustusinghighLDLasacriterionforprescription,somepatientsarereceivingstatintreatmentwhodonotneedit,andthosewithlowHDLandhighLDLwhodone

edthetreatmentarenotgettingit!”GerdAssmann,InstituteofClinicalChemistryandLabMedicine,Münster,GermanyTheLipidTriad-ExpertComments

TheImpactofGuidelinesPartVTheLipidTriad-WhattheNCEP*GuidelinesSayHDLCholesterol35mg/dl(0.9mmol/l)LDLCholesterol100mg/dl(2.6mmol/l)

TG200mg/dl(2.3mmol/l)*NationalCholesterolEducationProgramtargetsforsecondarypreventionTheLDL/HDLRatio-WhattheGuidelinessaySecondaryPreventionGuid

elinesNCEP(USA)LDL/HDL<2.8AssociationofCardiology(Germany)LDL/HDL<2.5SocietyofLipidTherapy(Germany)LDL/HDL<3CerivastatinClinicalDataPartVICha

ngeinLDL/HDLRatioDatapoolanalysis,8weeks00.511.522.533.544.55Baseline0.1mg0.2mg0.3mg0.4mg0.8mgn=459n=636n=645n=1072n=732LDL/HDLRatioDatao

nfile5045403530252015105025.60.746.240.235.532.0%ChangeinLDL/HDLRatioDatapoolanalysis,8weeks%ChangeinLDL/HDLRatioPlacebo0.1mg0.

2mg0.3mg0.4mg0.8mgDataonfileBaselineLDL/HDLratioAfter8weeks%ofrespondents5512.3369.9=318.13-=550.

2311.4=388.5=330.5=399.5LDL/HDLResponderRates0.4mgresponderrateat8weeks(n=941)DataonfileBaselineafter8weeksLDL/HDLMovingpatientsi

ntothesafetyareaafter8weeks(n=187)ReachingTargetwithLDL/HDLRatioReductionOSEetal.CurrMedRes&Opinion2000;16(2

):80-87LDL-C(mean%changefrombaselineafter24weeks)10-40-30-20-100-50-44.4%Men(n=200)Women(n=102)-37.0%LDLCholesterolReductionFromBaselineOSEeta

l.CurrMedRes&Opinion1999;15(3):231-43LDLReductionwith0.4mgofCerivastatin908070605040302010029.787.470.749.530354045Cumulative%o

frespondentsLDLResponderRateswith0.4mgLDL%reductionratesinpatientsaged60to65years(n=156)Dataonfile0,02,04,06,08,010

,012,014,016,018,0<50<40<30HDLbaselineHDLResponderRates>50%HDLincreaseDataonfile0.4mgresponderrateat8weeks6.510.317.98.29080706050403

0201001023.39.381.465.155.820304050TGresponderratesfor0.4mgTG%reductionratesfrombaseline300mg/dlat8weeks(n=43)Cumulative%ofrespondent

sDataonfileTriglyceridemean%changefrombaselineafter8weeks-20-100-30-405placebo0.3mg0.4mg<150mg/dl150-250mg/dl>250mg

/dl0.1mg0.2mg10-35-25-155TGReductionSTEINEetal.Atherosclerosis1999;144(S1):A37ApoB/ApoA1(LS-Means%Changewithminimum8weekstreatment

)-20,0-10,00,0-30,0-40,05Placebo-35,0-25,0-15,05,0ApoB/ApoA1CerivastatinPooledDataDataonfile0.1mg0.2mg0.3mg0.4mg0.8mgn=

588n=259n=265n=573n=658n=5992,0-18.5-22.4-26.8-29.1-36.0PatientGroupCerivastatinPlacebo100mg200mg300mg400mg800mg-1

8.5-16.9-21.0-19.6-17.2-21.9-20.5-22.8-22.4-20.6-24.9-23.0-21.2-26.0-24.9-26.6-26.8-25.9-28.3-25.5-26.0-29.5-28.7-30.3-29.1-2

8.0-30.6-23.2-29.1-30.7-27.5-33.2-36.0-35.3-37.1-32.3-35.9-37.1-36.0-38.5AllMaleFemale40Years>40-<65Years65Ye

arsElderlypatients-male-female2.02.21.7-0.52.71.11.21.0CerivastatinStudies8WeeksMinimumTreatmentApoB/ApoA1(%chang

eatweek8)DataonfileSalessupportingactivitiesActivelycreatingdataandinformationGainingconsensusfromOLLeadinginsteadofFollow

ingDatabaseLDL/HDLratioOpinionLeadersPrivateCardiologistsGPsSpreadingtheStory-EffectivelyPressInternetPublications