現(xiàn)代脂質(zhì)三聯(lián)治療

1、會計學(xué)1現(xiàn)代脂質(zhì)三聯(lián)治療現(xiàn)代脂質(zhì)三聯(lián)治療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 ris

2、k factor,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 ef

3、ficacy Its 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

4、 T (unpublished) HDL Intervention Trial (VA-HIT)RUBINS HB et al.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 TriglyceridesPercent change compared to placebo at 1 yearSecondary Prevention in 2531 menwith low HDL-C & LDL-C showed a22% reduction in combined fa

5、taland non-fatal MIHDL - Cholesterol 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 16

6、0 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 10085654525HDL-Cholesterol(mg/dl)LDL Cholesterol (mg/dL)0246810121416LDL5HDL=1.08 HDL1.08LDL/HDL5Incidence of cardiac events (per 1000 person-years)Gem

7、fibrozilPlaceboLDL-C Tertiles (mmol/L)HDL-C Tertiles (mmol/L)LDL-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

8、 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 0.88890.8898-1.02051.0252 3.77423.7744-4.40964.4101GOTTO A et al. Circulation 2000; 101: 477-484LDL/HDL Ratio as Therapeutic SuccessPlaceboStatin 2411631245050100

9、150200250300 5LDL / HDL - RatioTriglycerides = 200 mg/dlCAD cases per 1,000 subjects 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

10、 according to LDL/HDL ratio at baselineASSMANN G; Lipid Metabolism Disorders and CHD; 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

11、(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: 41PROCAM Heart Study Predictive value of risk factors for developing atheroscleroticCHD within 6 yearsVariable Risk RatioPredictive Power %TG 2

12、00 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 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 =

13、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 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 yea

14、rs020406080100120140 135135 - 154 155 - 195 195LDL-C (mg/dL)54301631120ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag, 1993: 60PROCAM Heart Study Expert OpinionsPart IVThe Lipid Triad - Expert Comments AHA, November 1999“Evaluating the risk on the bases of LDL alone, is naive” Val

15、entin 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 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 t

16、he Framingham Study and recently the VA-HIT Study.”Sander Robins, University Medical Center, Boston“Landmark statin trials have shown consistent benefits on CHDreduction after raising HDL by 5 - 10% irrespective of LDL levels”Christie Ballantyne, Baylor College of Medicine, Houston The Lipid Triad -

17、 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: 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 o

18、fcardiac events”Gerd Assmann, Lipid Metabolism Disorders and Coronary Heart Disease,MMV Medizin Verlag, 1993The Lipid Triad - Expert Comments PROCAM“The greatest difference, in relative terms, between the groupswith and without major coronary events was seen in theLDL/HDL-ratio”Assmann G, Cullen P a

19、nd 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, (cholesterol, triglycerides, LDL and HDL cholesterol) rather than cholesterol or LDL cholesterol determinants alone”

20、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 Triad should form the bases of diagnostic and therapeutic decisions in lipid therapy” Markolf Hanefeld, Institute for

21、 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 andhigh LDL who do need the treatment are not getting it!”Gerd Assmann, Institute of Clinical Chemistry and Lab

22、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 ( 2.6 mmol/l)TG 200 mg/dl (2.3 mmol/l)* National Cholesterol Education Program targets for secondar

23、y 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 riskMediumCHD riskLow CHD risk8%60%32%90%9%1%3-53LDL / HDLMoving patients into the safety ar

24、ea 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 Cholesterol Reduction From BaselineOSE et al. Curr Med Res &a

25、mp; 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 file0,02,04,06,08,010,012,014,016,018,0504050% HDL

26、 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 fileTriglyceride mean % change from baseline afte

27、r 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 B/ Apo A1 Cerivastatin P

28、ooled 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 -22.4-20.6-24.9-23.0-21.2-26.0-24.9-26.6-26.8-25.9-28.3-25.5-26.0-29.5-

29、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 ac

30、tivitiesActively creatingdata and informationGaining consensus from OLLeading instead of FollowingDatabase LDL/HDL ratioOpinion LeadersPrivate CardiologistsGPsSpreading the Story - EffectivelyPress Internet PublicationsEfficacy - The Power to Reach TargetLDL ReductionTGHDLLDL/HDL RatioThe Lipid Tria

31、d Supporting 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) 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