现代脂质三联治疗-课件.ppt

1、现代脂质三联治疗现代脂质三联治疗IntroductionPart IEfficacy -The Power to Reach TargetLDL ReductionTGHDLLDL/HDL RatioThe Lipid Triad The LDL/HDL Ratio-Our Strength,Our Story!Clear positioningfor LipobayA new perception of efficacyDifferentiation to AtorvastatinFit with our product profileLDLHDLAdditional risk factor

2、,especially in diabeticsThe Lipid Triad-OverviewTGThe Lipid TriadThe RatioThe Lipid Triad and Strategic Rationale Part II No scientific evidence Evidence contradicting this statement A marketing hypothesis to build their LDL story Creating the perception of the statin with the strongest efficacy Its

3、 logicalIts measurableIts practicableThe Lipid Triad -The GPs PerspectiveSupporting Data from Landmark StudiesPart III121086420%MortalityPlacebo Q1 Q2 Q3 Q4(low HDL-increase)(high HDL-increase)4S-StudyCAD Mortality per Quartiles of Increases in HDL-CholesterolKJEKSHUS J&PEDERSEN T(unpublished)HDL In

4、tervention Trial(VA-HIT)RUBINS HB et al.New Engl J Med 1999;341:41006-31-4-35-30-25-20-15-10-50510Cholesterol LDL-C HDL-C TriglyceridesPercent change compared to placebo at 1 yearSecondary Prevention in 2531 menwith low HDL-C&LDL-C showed a22%reduction in combined fataland non-fatal MIHDL-Cholestero

5、l as Risk Factor for CHDLRC-CPPT(Placebo)MRFIT(usual care)Incidence rate of CHDIncidence rate of CHD121086420100 130 160 190GORDON DJ et al.Circulation 1989;79:8-15.HDL-Cmg/dl65554535LDL-Cholesterol mg/dlLDL-Cholesterol mg/dl121086420100 130 160 19000.511.522.53Framingham Heart StudyCAD risk as a fu

6、nction of LDL-C and HDL-C in men(50 to 70 y)CASTELLI WP.Am J Cardiol 1998;82:60-65220 160 10085654525HDL-Cholesterol(mg/dl)LDL Cholesterol(mg/dL)0246810121416LDL5HDL=1.08 HDL1.08LDL/HDL5Incidence of cardiac events(per 1000 person-years)GemfibrozilPlaceboLDL-C Tertiles(mmol/L)HDL-C Tertiles(mmol/L)LD

7、L-C/HDL-C Tertiles244632 3634 4522 3938 5318 29Incidence for cardiac events vs lipid parameterHelsinki Heart StudyMANNINEN V,Leena T,Koskinen P et al.Circulation 1992;85:37-45AFCAPS/TEXCAPS Apo B/A1 Tertiles LDL-C/HDL-C Tertiles 1.6 1.4 1.210.8 0.6 0.4 0.2 0 1.6 1.4 1.210.8 0.6 0.4 0.2 0 Event Rate

8、per 100 Patient-Years of RiskEvent Rate per 100 Patient-Years of Risk 0.88890.8898-1.02051.0252 3.77423.7744-4.40964.4101GOTTO A et al.Circulation 2000;101:477-484LDL/HDL Ratio as Therapeutic SuccessPlaceboStatin 2411631245050100150200250300 5LDL/HDL-RatioTriglycerides=200 mg/dlCAD cases per 1,000 s

9、ubjects in 6 yearsASSMANN G and SCHULTE H;Am J Cardiol 1992;70:733-737Incidence of CAD vs LDL/HDL ratio by TG level(n=4559)PROCAM Heart Study 0501001502002503003 4 567LDL/HDL ratioCHD Incidence/1000 in 6 yearsCHD risk according to LDL/HDL ratio at baselineASSMANN G;Lipid Metabolism Disorders and CHD

10、;MMV Medizin Verlag,1993:435HighCHD risk3-53PROCAM Heart Study Mean values for developing atherosclerotic CHD within 6 yearsVariable CHD Development No CHD Development (n=186)(n=4221)TC(mg/dl)251.8222.9HDL-C(mg/dl)39.5 45.2LDL-C(mg/dl)176.2 147.1LDL/HDL ratio 4.72 3.4TG(mg/dl)163.0134.5ASSMANN G;Lip

11、id Metabolism Disorders and CHD;MMV Medizin Verlag,1993:41PROCAM Heart Study Predictive value of risk factors for developing atheroscleroticCHD within 6 yearsVariable Risk RatioPredictive Power%TG 200 mg/dl2.3 7.5TC 250(mg/dl)2.8 8.3LDL-C 195(mg/dl)3.7 12.0LDL-C 155(mg/dl)3.3 7.1HDL-C 35(mg/dl)3.911

12、.0LDL/HDL ratio 56.416.5ASSMANN G;Lipid Metabolism Disorders and CHD;MMV Medizin Verlag,1993:43PROCAM Heart Study HDL as CHD risk factor showed 186 events,in men aged 40-60 years(n=4407)CHD Incidence per 1,000 in 6 years020406080100120140160 35 35-55 55HDL-C(mg/dL)1103021ASSMANN G;Lipid Metabolism D

13、isorders and CHD;MMV Medizin Verlag,1993:59PROCAM Heart Study LDL as CHD risk factor showed 177 eventsin men aged 40-60 years,(n=4263)CHD Incidence per 1,000 in 6 years020406080100120140 135135-154 155-195 195LDL-C(mg/dL)54301631120ASSMANN G;Lipid Metabolism Disorders and CHD;MMV Medizin Verlag,1993

14、:60PROCAM Heart Study Expert OpinionsPart IVThe Lipid Triad-Expert Comments AHA,November 1999“Evaluating the risk on the bases of LDL alone,is naive”Valentin Fuster,Mount Sinai Medical Center,New York“The LDL/HDL ratio is a much stronger predictor for the CHD risk than LDL alone”Paul Ridker,Brigham

15、Institute for Womens Hospital,BostonACCP,March 2000“Low HDL is a better indicator of CHD than high LDL as seen in epidemiological studies such as the Framingham Study and recently the VA-HIT Study.”Sander Robins,University Medical Center,Boston“Landmark statin trials have shown consistent benefits o

16、n CHDreduction after raising HDL by 5-10%irrespective of LDL levels”Christie Ballantyne,Baylor College of Medicine,Houston The Lipid Triad-Expert Comments Helsinki Heart Study“The LDL/HDL ratio was the best single predictor of cardiac events”Manninen V,Leena T,Koskinen P et al.Circulation 1992;85,1:

17、37“Patients in the placebo group with triglyceride levels of 200 mg/dland an LDL/HDL ratio of 5.0 had by far the highest incidence ofcardiac events”Gerd Assmann,Lipid Metabolism Disorders and Coronary Heart Disease,MMV Medizin Verlag,1993The Lipid Triad-Expert Comments PROCAM“The greatest difference

18、,in relative terms,between the groupswith and without major coronary events was seen in theLDL/HDL-ratio”Assmann G,Cullen P and Schulte H;Eur Heart Journal 1998,19 A2-A11“For practical purposes it appears advisable to base predictions for atherosclerotic CAD and treatment decision on a full lipid pr

19、ofile,(cholesterol,triglycerides,LDL and HDL cholesterol)rather than cholesterol or LDL cholesterol determinants alone”Gerd Assmann,Lipid Metabolism Disorders and Coronary Heart Disease,MMV Medizin Verlag,1993The Lipid Triad-Expert Comments State of the Art Conference,Berlin April 2000“The Lipid Tri

20、ad should form the bases of diagnostic and therapeutic decisions in lipid therapy”Markolf Hanefeld,Institute for Metabolism Disorders and Research,Dresden“By just using high LDL as a criterion for prescription,some patients are receiving statin treatment who do not need it,and those with low HDL and

21、high LDL who do need the treatment are not getting it!”Gerd Assmann,Institute of Clinical Chemistry and Lab Medicine,Mnster,GermanyThe Lipid Triad-Expert Comments The Impactof GuidelinesPart VThe Lipid Triad-What the NCEP*Guidelines Say HDL Cholesterol 35 mg/dl(0.9 mmol/l)LDL Cholesterol 100 mg/dl(2

22、.6 mmol/l)TG 200 mg/dl(2.3 mmol/l)*National Cholesterol Education Program targets for secondary preventionThe LDL/HDL Ratio-What the Guidelines say Secondary Prevention GuidelinesNCEP(USA)LDL/HDL 2.8Association of Cardiology(Germany)LDL/HDL 2.5Society of Lipid Therapy(Germany)LDL/HDL 5HighCHD riskMe

23、diumCHD riskLow CHD risk8%60%32%90%9%1%3-53LDL/HDLMoving patients into the safety area after 8 weeks(n=187)Reaching Target with LDL/HDL Ratio ReductionOSE et al.Curr Med Res&Opinion 2000;16(2):80-87LDL-C (mean%changefrom baseline after 24 weeks)10-40-30-20-100-50-44.4%Men(n=200)Women(n=102)-37.0%LDL

24、 Cholesterol Reduction From BaselineOSE et al.Curr Med Res&Opinion 1999;15(3):231-43LDL Reduction with 0.4 mg of Cerivastatin908070605040302010029.787.470.749.5 30 35 40 45Cumulative%of respondentsLDL Responder Rates with 0.4 mg LDL%reduction rates in patients aged 60 to 65 years(n=156)Data on file0

25、,02,04,06,08,010,012,014,016,018,0504050%HDL increaseData on file0.4 mg responder rate at 8 weeks6.510.317.98.29080706050403020100 1023.39.381.465.155.8 20 30 40 50TG responder rates for 0.4 mg TG%reduction rates from baseline 300 mg/dl at 8 weeks(n=43)Cumulative%of respondentsData on fileTriglyceri

26、de mean%change from baseline after 8 weeks-20-100-30-405placebo0.3mg0.4mgBaseline triglycerides250 mg/dl0.1mg0.2mg10-35-25-155TG Reduction STEIN E et al.Atherosclerosis 1999;144(S 1):A 37Apo B/Apo A1(LS-Means%Change with minimum 8 weeks treatment)-20,0-10,00,0-30,0-40,05Placebo-35,0-25,0-15,05,0Apo

27、B/Apo A1 Cerivastatin Pooled DataData on file0.1mg0.2mg0.3mg0.4mg0.8mgn=588n=259n=265n=573n=658n=5992,0-18.5-22.4-26.8-29.1-36.0Patient GroupCerivastatinPlacebo100m mg 200m mg 300m mg 400m mg 800m mg-18.5-16.9-21.0-19.6-17.2-21.9-20.5-22.8-22.4-20.6-24.9-23.0-21.2-26.0-24.9-26.6-26.8-25.9-28.3-25.5-

28、26.0-29.5-28.7-30.3-29.1-28.0-30.6-23.2-29.1-30.7-27.5-33.2-36.0-35.3-37.1-32.3-35.9-37.1-36.0-38.5AllMaleFemale 40 Years 40-65 Years 65 YearsElderly patients-male-female2.02.21.7-0.52.71.11.21.0Cerivastatin Studies 8 Weeks Minimum TreatmentApo B/Apo A1(%change at week 8)Data on fileSales supporting activitiesActively creatingdata and informationGaining consensus from OLLeading instead of FollowingDatabase LDL/HDL ratioOpinion LeadersPrivate CardiologistsGPsSpreading the Story-EffectivelyPress Internet Publications