现代脂质三联治疗.ppt

现代脂质三联治疗,Introduction,Part I,Efficacy-The Power to Reach Target,Key Factor:+Differentiators:LDL ReductionTGHDLLDL/HDL RatioThe Lipid Triad,The LDL/HDL Ratio-Our Strength,Our Story!,A new perception of efficacy,LDL,HDL,Additional risk factor,especially in diabetics,The Lipid Triad-Overview,TG,The Lipid Triad,The Ratio,The 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,The lower.the better?,Its logical,Its measurable,Its practicable,The Lipid Triad-The GPs Perspective,HDL,LDL,Supporting Data from Landmark Studies,Part III,121086420,%Mortality,Placebo Q1 Q2 Q3 Q4(low HDL-increase)(high HDL-increase),4S-Study,CAD Mortality per Quartiles of Increases in HDL-Cholesterol,KJEKSHUS J&PEDERSEN T(unpublished),HDL Intervention Trial(VA-HIT),RUBINS HB et al.New Engl J Med 1999;341:410,0,6,-31,-4,-35,-30,-25,-20,-15,-10,-5,0,5,10,Cholesterol LDL-C HDL-C Triglycerides,Percent change compared to placebo at 1 year,Secondary Prevention in 2531 menwith low HDL-C&LDL-C showed a22%reduction in combined fataland non-fatal MI,HDL-Cholesterol as Risk Factor for CHD,LRC-CPPT(Placebo),MRFIT(usual care),Incidence rate of CHD,Incidence rate of CHD,121086420,100 130 160 190,GORDON DJ et al.Circulation 1989;79:8-15.,HDL-Cmg/dl65554535,LDL-Cholesterol mg/dl,LDL-Cholesterol mg/dl,121086420,100 130 160 190,0,0.5,1,1.5,2,2.5,3,Framingham Heart Study,CAD risk as a function of LDL-C and HDL-C in men(50 to 70 y),CASTELLI WP.Am J Cardiol 1998;82:60-65,220 160 100,85,65,45,25,HDL-Cholesterol(mg/dl),LDL Cholesterol(mg/dL),0,2,4,6,8,10,12,14,16,LDL=5,LDL5,HDL=1.08,HDL1.08,LDL/HDL=5,LDL/HDL5,Incidence of cardiac events,(per 1000 person-years),Gemfibrozil,Placebo,LDL-C Tertiles(mmol/L),HDL-C Tertiles(mmol/L),LDL-C/HDL-C Tertiles,Incidence for cardiac events vs lipid parameter,Helsinki Heart Study,MANNINEN V,Leena T,Koskinen P et al.Circulation 1992;85:37-45,AFCAPS/TEXCAPS,Apo B/A1 Tertiles,LDL-C/HDL-C Tertiles,1.6,1.4,1.2,1,0.8,0.6,0.4,0.2,0,1.6,1.4,1.2,1,0.8,0.6,0.4,0.2,0,Event Rate per 100 Patient-Years of Risk,Event Rate per 100 Patient-Years of Risk,0.8889,0.8898-1.0205,1.0252,3.7742,4.4101,GOTTO A et al.Circulation 2000;101:477-484,LDL/HDL Ratio as Therapeutic Success,Placebo,Statin,24,116,31,245,0,50,100,150,200,250,300,=5,5,LDL/HDL-Ratio,Triglycerides 200 mg/dl,Triglycerides=200 mg/dl,CAD cases per 1,000 subjects in 6 years,ASSMANN G and SCHULTE H;Am J Cardiol 1992;70:733-737,Incidence of CAD vs LDL/HDL ratio by TG level(n=4559),PROCAM Heart Study,0,50,100,150,200,250,300,3,4,5,5,6,7,LDL/HDL ratio,CHD Incidence/1000 in 6 years,CHD risk according to LDL/HDL ratio at baseline,ASSMANN G;Lipid Metabolism Disorders and CHD;MMV Medizin Verlag,1993:43,5,HighCHD risk,MediumCHD risk,Low CHD risk,3-5,3,PROCAM Heart Study,Mean values for developing atherosclerotic CHD within 6 years,Variable 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)163.0134.5,ASSMANN G;Lipid Metabolism Disorders and CHD;MMV Medizin Verlag,1993:41,PROCAM Heart Study,Predictive value of risk factors for developing atheroscleroticCHD within 6 years,Variable 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 56.416.5,ASSMANN G;Lipid Metabolism Disorders and CHD;MMV Medizin Verlag,1993:43,PROCAM 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 years,0,20,40,60,80,100,120,140,160,35 35-55 55,HDL-C(mg/dL),110,30,21,ASSMANN G;Lipid Metabolism Disorders and CHD;MMV Medizin Verlag,1993:59,PROCAM Heart Study,LDL as CHD risk factor showed 177 eventsin men aged 40-60 years,(n=4263),CHD Incidence per 1,000 in 6 years,0,20,40,60,80,100,120,140,135135-154 155-195 195,LDL-C(mg/dL),54,30,16,31,120,ASSMANN G;Lipid Metabolism Disorders and CHD;MMV Medizin Verlag,1993:60,PROCAM Heart Study,Expert Opinions,Part IV,The 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 Institute for Womens Hospital,Boston,ACCP,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 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;85,1:37“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,1993,The 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 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,(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,1993,The 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 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 Medicine,Mnster,Germany,The Lipid Triad-Expert Comments,The Impactof Guidelines,Part V,The 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 secondary prevention,The 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 3,CerivastatinClinical Data,Part VI,Change in LDL/HDL Ratio,Datapool analysis,8 weeks,0,0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,Baseline,0.1mg,0.2mg,0.3mg,0.4mg,0.8mg,n=459,n=636,n=645,n=1072,n=732,LDL/HDL Ratio,Data on file,50,45,40,35,30,25,20,15,10,5,0,25.6,0.7,46.2,40.2,35.5,32.0,%Change in LDL/HDL Ratio,Datapool analysis,8 weeks,%Change in LDL/HDL Ratio,Placebo,0.1mg,0.2mg,0.3mg,0.4mg,0.8mg,Data on file,Baseline LDL/HDL ratio After 8 weeks%of respondents 5 5 12.3 3 69.9=3 18.1 3-=5 5 0.2 3 11.4=3 88.5=3 3 0.5=3 99.5,LDL/HDL Responder Rates,0.4 mg responder rate at 8 weeks(n=941),Data on file,Baseline,after 8 weeks,5,HighCHD risk,MediumCHD risk,Low CHD risk,8%,60%,32%,90%,9%,1%,3-5,3,LDL/HDL,Moving patients into the safety area after 8 weeks(n=187),Reaching Target with LDL/HDL Ratio Reduction,OSE et al.Curr Med Res 16(2):80-87,LDL-C(mean%changefrom baseline after 24 weeks),10,-40,-30,-20,-10,0,-50,-44.4%,Men(n=200),Women(n=102),-37.0%,LDL Cholesterol Reduction From Baseline,OSE et al.Curr Med Res 15(3):231-43,LDL Reduction with 0.4 mg of Cerivastatin,90,80,70,60,50,40,30,20,10,0,29.7,87.4,70.7,49.5,30,35,40,45,Cumulative%of respondents,LDL Responder Rates with 0.4 mg,LDL%reduction rates in patients aged 60 to 65 years(n=156),Data on file,0,0,2,0,4,0,6,0,8,0,10,0,12,0,14,0,16,0,18,0,50,40,30,HDL baseline,HDL Responder Rates,50,%HDL increase,Data on file,0.4 mg responder rate at 8 weeks,6.5,10.3,17.9,8.2,90,80,70,60,50,40,30,20,10,0,10,23.3,9.3,81.4,65.1,55.8,20,30,40,50,TG responder rates for 0.4 mg,TG%reduction rates from baseline 300 mg/dl at 8 weeks(n=43),Cumulative%of respondents,Data on file,Triglyceride mean%change from baseline after 8 weeks,-20,-10,0,-30,-40,5,placebo,0.3mg,0.4mg,Baseline triglycerides,150 mg/dl,150-250 mg/dl,250 mg/dl,0.1mg,0.2mg,10,-35,-25,-15,5,TG Reduction,STEIN E et al.Atherosclerosis 1999;144(S 1):A 37,Apo B/Apo A1(LS-Means%Change with minimum 8 weeks treatment),-20,0,-10,0,0,0,-30,0,-40,0,5,Placebo,-35,0,-25,0,-15,0,5,0,Apo B/Apo A1 Cerivastatin Pooled Data,Data on file,0.1mg,0.2mg,0.3mg,0.4mg,0.8mg,n=588,n=259,n=265,n=573,n=658,n=599,2,0,-18.5,-22.4,-26.8,-29.1,-36.0,Patient Group,Cerivastatin,Placebo,100mg 200mg 300mg 400mg 800mg,-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,-26.8-25.9-28.3-25.5-26.0-29.5-28.7-30.3,-29.1-28.0-30.6-23.2-29.1-30.7-27.5-33.2,-36.0-35.3-37.1-32.3-35.9-37.1-36.0-38.5,AllMaleFemale 40 Years 40-65 Years 65 YearsElderly patients-male-female,2.02.21.7-0.52.71.11.21.0,Cerivastatin Studies 8 Weeks Minimum Treatment,Apo B/Apo A1(%change at week 8),Data on file,Sales supporting activities,Actively creatingdata and information,Gaining consensus from OL,Leading instead of Following,Database LDL/HDL ratio,Opinion Leaders,Private Cardiologists,GPs,Spreading the Story-Effectively,Press Internet Publications,