《现代脂质三联治疗》演示PPT

1、现代脂质三联治疗现代脂质三联治疗 Introduction Part I Efficacy - The Power to Reach Target LDL ReductionTG HDL LDL/HDL Ratio The Lipid Triad The LDL/HDL Ratio - Our Strength, Our Story! Clear positioning for Lipobay A new perception of efficacy Differentiation to Atorvastatin Fit with our product profile LDLHDL Addi

2、tional 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

3、the strongest efficacy Its logical Its measurable Its practicable The Lipid Triad - The GPs Perspective Supporting Data from Landmark Studies Part III 12 10 8 6 4 2 0 % Mortality Placebo Q1 Q2 Q3 Q4 (low HDL-increase) (high HDL-increase) 4S - Study CAD Mortality per Quartiles of Increases in HDL-Cho

4、lesterol KJEKSHUS J 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 men with low HDL-C 79: 8 - 15. HDL - C mg / dl 65 55 45 35 LDL - Cholesterol mg / dlLDL - Cholesterol mg / dl 12 10

5、 8 6 4 2 0 100 130 160 190 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 LDL5HDL=1.08 HDL1.08LDL/HDL5 Inci

6、dence of cardiac events (per 1000 person-years) GemfibrozilPlacebo LDL-C Tertiles (mmol/L)HDL-C Tertiles (mmol/L) LDL-C/HDL-C Tertiles 2446 32 3634 4522 3938 5318 29 Incidence for cardiac events vs lipid parameter Helsinki Heart Study MANNINEN V, Leena T, Koskinen P et al. Circulation 1992; 85: 37-4

7、5 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 0.88890.8898- 1.0205 1.0252 3.77423.7744- 4.4096 4.4101 GOTTO A et al. Circulation 2000; 101: 477-

8、484 LDL/HDL Ratio as Therapeutic Success Placebo Statin 24 116 31 245 0 50 100 150 200 250 300 5LDL / HDL - Ratio 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

9、Heart Study 0 50 100 150 200 250 300 3 4 567 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 High CHD risk 3-53 PROCAM Heart Study Mean values for developing atherosclerotic CHD

10、within 6 years Variable CHD Development No CHD Development (n = 186)(n = 4221) TC (mg/dl)251.8222.9 HDL-C (mg/dl) 39.5 45.2 LDL-C (mg/dl) 176.2 147.1 LDL/HDL ratio 4.72 3.4 TG (mg/dl)163.0134.5 ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag, 1993: 41 PROCAM Heart Study Predictive

11、value of risk factors for developing atherosclerotic CHD within 6 years Variable Risk RatioPredictive Power % TG 200 mg/dl2.3 7.5 TC 250 (mg/dl)2.8 8.3 LDL-C 195 (mg/dl) 3.7 12.0 LDL-C 155 (mg/dl) 3.3 7.1 HDL-C 35 (mg/dl) 3.911.0 LDL/HDL ratio 56.416.5 ASSMANN G; Lipid Metabolism Disorders and CHD;

12、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, 19

13、93: 59 PROCAM Heart Study LDL as CHD risk factor showed 177 events in 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 3016 31 120 ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag, 1993: 60

14、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

15、, 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 con

16、sistent benefits on CHD reduction 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

17、 P et al. Circulation 1992;85, 1: 37 “ Patients in the placebo group with triglyceride levels of 200 mg/dl and an LDL/HDL ratio of 5.0 had by far the highest incidence of cardiac events” Gerd Assmann, Lipid Metabolism Disorders and Coronary Heart Disease, MMV Medizin Verlag, 1993 The Lipid Triad - E

18、xpert Comments PROCAM “The greatest difference, in relative terms, between the groups with and without major coronary events was seen in the LDL/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 athero

19、sclerotic 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 Co

20、mments 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

21、 receiving statin treatment who do not need it, and those with low HDL and high 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 Impact of Guidelines Part V The Lipid Triad - What

22、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 Guidelines NCEP (USA) LDL/HDL

23、2.8 Association of Cardiology (Germany) LDL/HDL 2.5 Society of Lipid Therapy (Germany) LDL/HDL 5 High CHD risk Medium CHD 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 M

24、ed Res 16 (2):80-87 LDL-C (mean % change from 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.

25、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 50405 0 % HDL increase Data on file 0.4 mg responder rate at 8 weeks 6.5 10.3 17.9 8.2 90 80 7

26、0 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 0.3mg0.4mg Baseline triglycerides 250 mg/dl 0.1mg0.2mg 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 Po