现代脂质三联治疗课件

1、1现代脂质三联治疗现代脂质三联治疗2introductionpart i3efficacy - the power to reach targetldl reductiontghdlldl/hdl ratiothe lipid triad 4the ldl/hdl ratio - our strength, our story!clear positioningfor lipobaya new perception of efficacydifferentiation to atorvastatinfit with our product profile5ldlhdladditional ri

2、sk factor,especially in diabeticsthe lipid triad - overviewtgthe lipid triadthe ratio6the lipid triad and strategic rationale part ii7 no scientific evidence evidence contradicting this statement a marketing hypothesis to build their ldl story creating the perception of the statin with the strongest

3、 efficacy8 its logicalits measurableits practicablethe lipid triad - the gps perspective9hdlldl10supporting data from landmark studiespart iii11121086420% mortalityplacebo q1 q2 q3 q4(low hdl-increase) (high hdl-increase)4s - studycad mortality per quartiles of increases in hdl-cholesterolkjekshus j

4、 & pedersen t (unpublished) 12hdl intervention trial (va-hit)rubins hb et al.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% reducti

5、on in combined fataland non-fatal mi13hdl - 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 / dl

6、121086420100 130 160 1901400.511.522.53framingham 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)150246810121416ldl5hdl=1.08 hdl1.08ldl/hdl5incidence of cardiac events (pe

7、r 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 parameterhelsinki heart studymanninen v, leena t, koskinen p et al. circulation 1992; 85: 37-4516afcaps/texcaps apo b/a1 tertiles

8、 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 0.88890.8898-1.02051.0252 3.77423.7744-4.40964.4101gotto a et al. circulation 2000; 101: 477-484ldl/hdl ratio as therapeutic successplace

9、bostatin 172411631245050100150200250300 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 180501001502002503003 4 567ldl/hdl ratiochd inci

10、dence/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 19mean values for developing atherosclerotic chd within 6 yearsvariable chd development no chd development (n = 186)(n =

11、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: 41procam heart study 20predictive value of risk factors for developing atheroscleroticchd within 6 yearsvariable

12、 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 metabolism disorders and chd; mmv medizin verlag, 1993: 43procam heart study 21hdl as chd risk factor showed 186 even

13、ts, 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 verlag, 1993: 59procam heart study 22ldl as chd risk factor showed 177 eventsin men aged 40 - 60 years, ( n = 4

14、263)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: 60procam heart study 23expert opinionspart iv24the lipid triad - expert comments aha, november 1999“evaluating the risk

15、 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, boston25accp, march 2000“low hdl is a better indicator of chd than high ldl a

16、s 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 col

17、lege of medicine, houston the lipid triad - expert comments 26helsinki 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 ra

18、tio 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 27procam“the greatest difference, in relative terms, between the groupswith and without major coronary events was

19、 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 cho

20、lesterol or ldl cholesterol determinants alone”gerd assmann, lipid metabolism disorders and coronary heart disease,mmv medizin verlag, 1993the lipid triad - expert comments 28state of the art conference, berlin april 2000“the lipid triad should form the bases of diagnostic and therapeutic decisions

21、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

22、assmann, institute of clinical chemistry and lab medicine, mnster, germanythe lipid triad - expert comments 29the impactof guidelinespart v30the 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)* nation

23、al cholesterol education program targets for secondary prevention31the 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

24、%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):80-8737ldl-c (mean % changefrom baseline after 24 weeks) 10-40-30-20-100-50-44.4%men( n = 200)women( n = 102)-37.0%ldl chol

25、esterol reduction from baselineose et al. curr med res & opinion 1999; 15 (3): 231-43ldl reduction with 0.4 mg of cerivastatin38908070605040302010029.787.470.749.5 30 35 40 45cumulative % of respondentsldl responder rates with 0.4 mg ldl % reduction rates in patients aged 60 to 65 years (n = 156

26、)data on file390,02,04,06,08,010,012,014,016,018,0504050% hdl increasedata on file0.4 mg responder rate at 8 weeks6.510.317.98.2409080706050403020100 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 file41triglyceride 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 3742apo b/apo a1 (ls-means % change with minimum 8 weeks treatment)-20,