1、Angiographic and Clinical Event TrialsnCholesterol Lowering Atherosclerosis Study(CLAS)1nDiet and niacin+colestipol(vs diet and placebo)n188 men(aged 4059 y),post-CABGnNonsmokers or former smokers,nondiabetic,nonhypertensivenTotal-C at entry:185350 mg/dL;drug responsivenFamilial Atherosclerosis Trea
2、tment Study(FATS)2 nLovastatin+colestipol,niacin+colestipol,or conventional therapyn146 men(aged 62 y)with CAD and family history of CADnApoB 125 mg/dLnAverage stenosis:34%1.Blackenhorn DH et al.JAMA.1987;257:323332402.Brown G et al.N Engl J Med.1990;323:12891298%changeTrial LDL-C HDL-C TGCLAS Place
3、bo(2 y)1 5*2 5*Niacin+colestipol(2 y)1 43*37*22*Niacin+colestipol(4 y)2 40 37 18FATS(2.5 y)3 Conventional 7*6*15 Niacin+colestipol 32*41*29*Lovastatin+colestipol 45*16 9Versus baseline:*P 0.001;P 0.01;*P 0.05;Versus placebo:P 0.001;P 0.03 1.Blankenhorn DH et al.JAMA 1987;257:323332402.Cashin-Hemphil
4、l L et al.JAMA 1990;264:301330173.Brown BG et al.N Engl J Med 1990;323:12891298 Mean(mg/dL)PredictorProgressorNonprogressorP valuePlacebo(n=82:49 progressors,33 nonprogressors)ApoB1281160.03ApoC-III(total)12.410.30.03ApoC-III(HS)*5.94.90.03Drug(n=80:31 progressors,49 nonprogressors)ApoC-III(HS)*6.47
5、.50.05*HS=heparin supernate(apoC-III in HDL)Blankenhorn DH et al.Circulation 1990;81:470476PredictorrP valueApoB 0.38 0.0001LDL-C0.27 0.01HDL-C-0.33 0.001ApoA-I-0.28 Not reportedBrown G et al.N Engl J Med 1990;323:12891298nBezafibrate Coronary Atherosclerosis Intervention Trial(BECAIT)1nBezafibrate
6、vs placebon92 male survivors of MI,aged 45 y at time of eventnCoronary angiography at baseline and after 2 and 5 ynLopid Coronary Angiography Trial(LOCAT)2nGemfibrozil vs placebon395 men,post-CABGnCoronary angiography at baseline and after 32 mos1.Ericsson CG et al.Lancet 1996;347:8498532.Frick MH e
7、t al.Circulation 1997;96:21372143Change from baseline:*P 0.001;P=0.551;*P=0.020Bez=bezafibrate 200 mg TID(n=42);Plac=placebo(n=39)Ericsson CG et al.Lancet 1996;347:849853-14.0*-3.58.6*-26.3*-5.6-2.2-0.82.7-30-25-20-15-10-50510Total-CLDL-CHDL-CTotal-TG Bez Plac(266)(267)Medianbaseline(mg/dL):Bez Plac
8、(180)(179)BezPlac(34)(39)Bez Plac(216)(175)Median%change from baseline15-35*P 0.001 for between-group difference and for change from baselineFrick MH et al.Circulation 1997;96:21372143-5.5*-4.5*21*-36*5.15.37.04.6-40-30-20-100102030Total-CLDL-CHDL-CTGGemfibrozilPlaceboMean%change from baselinenLipop
9、rotein and Coronary Atherosclerosis Study(LCAS)nFluvastatin versus placebo in patients with low versus higher HDL-C nAngiographic data from 339 patients:n 68 with baseline HDL-C 35 mg/dLn 271 with baseline HDL-C 35 mg/dLBallantyne CM et al.Circulation 1999;99:7367430.300.250.200.150.100.050HDL-C 35
10、mg/dLHDL-C 35 mg/dLFluvastatinPlaceboDecrease in minimum lumen diameter(mm)P=0.09P=0.0004P for interaction=0.01Ballantyne CM et al.Circulation 1999;99:736743-0.065-0.274-0.036-0.0832.51.000.750.500.250.00012Probability of event-free survival1.000.750.500.250.000122.5Probability of event-free surviva
11、lFluvastatinFluvastatinPlaceboPlaceboHDL-C 35 mg/dLHDL-C 35 mg/dLP=0.002P=0.232Time(y)Time(y)Ballantyne CM et al.Circulation 1999;99:736743Trial(pts with Agent Baseline(mg/dL)%changeevaluable angiography)(dosage)LDL-C HDL-CLDL-C HDL-CBECAIT(N=81)Bezafibrate180 34 3.5 9(600 mg/d)LOCAT(N=372)Gemfibroz
12、il138 31 4.5 21(1,200 mg/d)LCAS(N=339)Fluvastatin146 43 25 9(40 mg/d)LCAS(HDL-CFluvastatin143 32 25 16 35 mg/dL)(40 mg/d)(N=68)Ballantyne CM et al.Circulation 1999;99:736743nPrimary-prevention,placebo-controlled trial to determine whether increasing HDL-C levels and decreasing LDL-C levels would red
13、uce incidence of CHDn4,081 dyslipidemic men,aged 4055 ynSubjects randomized to gemfibrozil(600 mg BID)or placebonStudy duration:5 yFrick MH et al.N Engl J Med.1987;317:12371245Numbers inside bars indicate number of cardiac events in each subgroupManninen V et al.Circulation.1992;85:3745Incidence of
14、cardiac events(per 1,000 person-years)05101520HDL-C 42HDL-C 42GemfibrozilPlacebo TG 200 TG 200 TG 200 TG 2002736791416823mg/dL:nRandomized,double-blind trial to compare lovastatin with placebo for prevention of first acute major coronary event in men and women without clinically evident atherosclero
15、tic CVDn5,608 men and 997 women with average Total-C and LDL-C and below-average HDL-CDowns JR et al.JAMA 1998;279:161516220.91.51.2-2.3-18.4-256-15-30-25-20-15-10-50510TCLDL-CHDL-CTGPercent change from baselinePlaceboLovastatin*P value 0.001 for all lipid parameters:between group differences and ch
16、anges on lovastatin from baseline to Year 1.Downs JR et al.JAMA 1998;279:16151622Copyright 1998,American Medical Association.No.at risk:LovastatinN=3,304N=3,270N=3,228 N=3,184N=3,134N=1,688PlaceboN=3,301N=3,251N=3,211 N=3,159N=3,092N=1,6440.070.060.050.040.030.020.010.000123455+Cumulative incidenceP
17、laceboLovastatin37%risk reducation(P 60 y)nStudy duration:7 ynMedian follow-up:5.1 ynPrimary end point:nonfatal MI or coronary deathRubins HB et al.N Engl J Med 1999;341:410418Rubins HB et al.N Engl J Med 1999;341:410418LDL-CHDL-CTCTG%change with gemfibrozil versus placebo-35-30-25-20-15-10-50510No
18、change+6-4-31*Investigator-designatedP=0.006;*P=0.04Rubins HB et al.N Engl J Med 1999;341:410418-30-25-20-15-10-50NonfatalMI/CHDdeathCHDdeathStroke*All-causemortality-22-22-29*-11 275/219118/9388/64220/198%decrease Placebo/Treated:nBezafibrate(400 mg/d)versus placebo n3,122 men and women with docume
19、nted CHDnMean age:60 y(range:4574 y)n78%with prior MInBaseline lipid parameters:TC 180250 mg/dL HDL-C 45 mg/dL LDL-C 180 mg/dL*TG 300 mg/dLnPrimary end point:fatal or nonfatal MI or sudden death*LDL-C 160 mg/dL in patients aged 50 yGoldbourt U et al.Am J Cardiol 1993;71:909915Goldbourt U et al.Eur H
20、eart J 1998;19:H42H47-4-512-22-25-20-15-10-5051015TC(212)LDL-C(148)HDL-C(35)TG(149)Baseline(mg/dL):%change from baselinePresented at European Society of Cardiology Meeting,Vienna,1998-9-40-45-40-35-30-25-20-15-10-50All patientsTG 200 mg/dLP=0.27P=0.03Relative risk reduction(%)Presented at European S
21、ociety of Cardiology Meeting,Vienna,1998nLong-term efficacy and safety of five lipid-influencing drugsnNiacin,clofibrate,dextrothyroxine,and two estrogen regimensn8,341 men(aged 3064 y)with previous MInInitial study conducted between 1966 and 1975(mean follow-up:6.2 y)nAt end of study,6,008 survivor
22、s followed for additional mean 8.8 yCanner PL et al.J Am Coll Cardiol 1986;8:12451255NiacinPlaceboP=0.00121009080706050403020100246810121416Years of follow-upSurvival(%)Canner PL et al.J Am Coll Cardiol 1986;8:12451255 nRandomized,double-blind,placebo-controlled trial to determine whether estrogens
23、plus progestin alter risk of CHD events in postmenopausal women with coronary diseasenCEE(0.625 mg/d)plus MPA(2.5 mg/d)versus placebon2,763 postmenopausal women(mean age:67 y)with coronary disease and intact uterus nAverage follow-up:4.1 ynPrimary end point:nonfatal MI or CHD deathCEE=conjugated equ
24、ine estrogen;MPA=medroxyprogesterone acetateHulley S et al.JAMA 1998;280:605613-20-15-10-5051015LDL-CHDL-CTGMean%change from baselinePlaceboEstrogen/progestin*P 0.001-3-14*-28*10*2Hulley S et al.JAMA 1998;280:605613.Copyright 1998,American Medical Association.1510500(2,763)1(2,631)2(2,506)3(2,392)4(
25、1,435)5(113)Incidence(%)Follow-up,y(No.at risk)Estrogen/progestinPlaceboHulley S et al.JAMA 1998;280:605613.Copyright 1998,American Medical Association.nIn angiographic trials,benefits were related to reductions in LDL-C(apoB-100)and increases in HDL-C(apoA-I).nFibrates have shown benefits in patien
26、ts with:nHigh TG and low HDL-C(Helsinki,BIP)nNormal LDL-C and low HDL-C(VA-HIT)nStatins have consistently shown the greatest benefits in patients with low HDL-C and average LDL-C(CARE,LIPID,AFCAPS/TexCAPS)or high LDL-C(4S,WOSCOPS).nIn risk assessment,should the cut point for low HDL-C be redefined(4
27、0 mg/dL in men and 45 mg/dL in women)?nIn therapy,should increasing HDL-C be more important in regard to target goals?nAre the clinical effects of raising HDL-C dependent on the effects on TG?nWill gene therapy for HDL-C and apoA-I become a reality?谢谢您的聆听与观看THANK YOU FOR YOUR GUIDANCE.感谢阅读！为了方便学习和使用，本文档的内容可以在下载后随意修改，调整和打印。欢迎下载！汇报人：XXX日期：20XX年XX月XX日
