《现代脂质三联治疗》ppt课件

1、Part IEfficacy - The Power to Reach Target The LDL/HDL Ratio - Our Strength, Our Story!Clear positioningfor LipobayA new perception of efficacyDifferentiation to AtorvastatinFit with our product profileLDLHDLAdditional risk factor,especially in diabeticsThe Lipid Triad - OverviewTGThe Lipid TriadThe

2、 RatioPart 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 logicalIts measurableIts practicableThe Lipid Triad - The GPs PerspectivePart III121086420% MortalityPlaceb

3、o 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(high HDL-increase)4S - StudyCAD Mortality per Quartiles of Increases in HDL-CholesterolKJEKSHUS J & PEDERSEN T (unpublished) HDL Intervention Trial (VA-HIT)RUBINS HB et al.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 Triglyc

4、eridesPercent 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 - Cholesterol as Risk Factor for CHDLRC - CPPT (Placebo)MRFIT (usual care)Incidence rate of CHDIncidence rate of CHD121086420100 130

5、 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 function of LDL-C and HDL-C in men (50 to 70 y)CASTELLI WP. Am J Cardiol 1998; 82:60-65220 160 100856

6、54525HDL-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)LDL-C/HDL-C Tertiles244632 3634 4522 3938 5318 29Incidence for cardiac events vs lipid paramet

7、erHelsinki 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 per 100 Patient-Years of RiskEvent Rate per 100 Patient-Years of Risk 0.88890.8898-1.02

8、051.0252 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 subjects in 6 yearsASSMANN G and SCHULTE H; Am J Cardiol 1992; 70: 733-737Incid

9、ence 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; MMV Medizin Verlag, 1993: 435HighCHD risk3-53PROCAM Heart Study Mean

10、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; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag, 1993

11、: 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) 3.911.0LDL/HDL ratio 56.416.5ASSMANN G; Lipid Metab

12、olism 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 Disorders and CHD; MMV Medizin V

13、erlag, 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 - 154 155 - 195 195LDL-C (mg/dL)54301631120ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag, 1993: 60PROCAM Heart Stu

14、dy Part 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 alonePaul Ridker, Brigham Institute for Womens Hospita

15、l, 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 on CHDreduction after rais

16、ing HDL by 5 - 10% irrespective of LDL levelsChristie 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 eventsManninen V, Leena T, Koskinen P et al. Circulation 1992;85, 1: 37“ Patients in

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

18、ve terms, between the groupswith and without major coronary events was seen in theLDL/HDL-ratioAssmann 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 profile,

19、(cholesterol, triglycerides, LDL and HDL cholesterol) rather than cholesterol or LDL cholesterol determinants aloneGerd 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 Tr

20、iad 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 HD

21、L andhigh 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 Part VThe Lipid Triad - What the NCEP * Guidelines Say HDL Cholesterol 35 mg/dl ( 0.9 mmol/l)LDL Cholesterol 100 mg/dl ( 2.6 mmo

22、l/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 ri

23、skMediumCHD 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 =

24、200)Women( n = 102)-37.0%LDL 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 patien

25、ts aged 60 to 65 years (n = 156)Data on file0,02,04,06,08,010,012,014,016,018,0504050% 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

26、= 43) Cumulative % of respondentsData on fileTriglyceride 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