HDL的临床试验优选课件

1、HDL and Coronary Heart DiseaseAngiographic and Clinical Event TrialsHDL and Coronary Heart DiseaseAngiographic Trials of Combination TherapyCholesterol Lowering Atherosclerosis Study (CLAS)1Diet and niacin + colestipol (vs diet and placebo)188 men (aged 4059 y), post-CABGNonsmokers or former smokers

2、, nondiabetic, nonhypertensiveTotal-C at entry: 185350 mg/dL; drug responsiveFamilial Atherosclerosis Treatment Study (FATS)2 Lovastatin + colestipol, niacin + colestipol, or conventional therapy146 men (aged 62 y) with CAD and family history of CADApoB 125 mg/dLAverage stenosis: 34% 1. Blackenhorn

3、DH et al. JAMA. 1987;257:323332402. Brown G et al. N Engl J Med. 1990;323:12891298Angiographic Trials of CombinAngiographic Trials of Combination Therapy Effects on Lipids % changeTrial LDL-CHDL-C TGCLAS Placebo (2 y)1 5* 2 5* Niacin + colestipol (2 y)1 43* 37* 22* Niacin + colestipol (4 y)2 40 37 1

4、8FATS (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-Hemphill L et al. JAMA 1990;264:301330173. Brown BG et al. N Engl

5、 J Med 1990;323:12891298Angiographic Trials of CombinCholesterol-Lowering Atherosclerosis Study (CLAS)Univariate Apo Predictors of Coronary Progression Mean (mg/dL)PredictorProgressorNonprogressorP valuePlacebo (n = 82: 49 progressors, 33 nonprogressors)ApoB1281160.03ApoC-III (total)12.410.30.03ApoC

6、-III (HS)*5.94.90.03Drug (n = 80: 31 progressors, 49 nonprogressors)ApoC-III (HS)* 6.47.50.05*HS = heparin supernate (apoC-III in HDL)Blankenhorn DH et al. Circulation 1990;81:470476Cholesterol-Lowering AtherosclFamilial Atherosclerosis Treatment Study (FATS)Univariate Predictors of Change in Proxim

7、al StenosisPredictorrP valueApoB0.38 0.0001LDL-C0.270.01HDL-C-0.330.001ApoA-I-0.28Not reportedBrown G et al. N Engl J Med 1990;323:12891298Familial Atherosclerosis TreatAngiographic Trials of Fibrate TherapyBezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT)1Bezafibrate vs placebo92 mal

8、e survivors of MI, aged 45 y at time of eventCoronary angiography at baseline and after 2 and 5 yLopid Coronary Angiography Trial (LOCAT)2Gemfibrozil vs placebo395 men, post-CABGCoronary angiography at baseline and after 32 mos1. Ericsson CG et al. Lancet 1996;347:8498532. Frick MH et al. Circulatio

9、n 1997;96:21372143Angiographic Trials of FibrateBezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) Effect on Lipid Levels at 5 YearsChange 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;347:8498

10、53-14.0*-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(180)(179)BezPlac(34)(39) Bez Plac(216)(175)Median % change from baseline15-35Bezafibrate Coronary AtherosclLopid Coronary Angiography Trial (LOCAT)Effect on Lipid L

11、evels at 1 Year*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 baselineLopid Coronary Angiography TriAngiographic Trial of Statin Ther

12、apyLipoprotein and Coronary Atherosclerosis Study (LCAS)Fluvastatin versus placebo in patients with low versus higher HDL-C Angiographic data from 339 patients: 68 with baseline HDL-C 35 mg/dL 271 with baseline HDL-C 35 mg/dLBallantyne CM et al. Circulation 1999;99:736743Angiographic Trial of Statin

13、 TLipoprotein and Coronary Atherosclerosis Study (LCAS) Benefit of Statin Therapy in Patients With Low HDL-C0.300.250.200.150.100.050HDL-C 35 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

14、:736743-0.065-0.274-0.036-0.083Lipoprotein and Coronary AtherLipoprotein and Coronary Atherosclerosis Study (LCAS)Event-Free Survival2.51.000.750.500.250.00012Probability of event-free survival1.000.750.500.250.000122.5Probability of event-free survivalFluvastatinFluvastatinPlaceboPlaceboHDL-C 35 mg

15、/dLHDL-C 35 mg/dLP = 0.002P = 0.232Time (y)Time (y)Ballantyne CM et al. Circulation 1999;99:736743Lipoprotein and Coronary AtheAngiographic Trials in Patients With Low HDL-CEffects on LipidsTrial (pts with Agent Baseline (mg/dL) % changeevaluable angiography) (dosage)LDL-C HDL-CLDL-C HDL-CBECAIT (N

16、= 81)Bezafibrate180 34 3.5 9(600 mg/d)LOCAT (N = 372)Gemfibrozil138 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;99:736743Angiographic Trials in PatientHelsinki Heart StudyPrimary

17、-prevention, placebo-controlled trial to determine whether increasing HDL-C levels and decreasing LDL-C levels would reduce incidence of CHD4,081 dyslipidemic men, aged 4055 ySubjects randomized to gemfibrozil (600 mg BID) or placeboStudy duration: 5 yFrick MH et al. N Engl J Med. 1987;317:12371245H

18、elsinki Heart StudyPrimary-prHelsinki Heart StudyIncidence of CHD EventsNumbers inside bars indicate number of cardiac events in each subgroupManninen V et al. Circulation. 1992;85:3745Incidence of cardiac events(per 1,000 person-years)05101520HDL-C 42HDL-C 42GemfibrozilPlacebo TG 200 TG 200 TG 200

19、TG 2002736791416823mg/dL:Helsinki Heart StudyIncidenceAir Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)Randomized, double-blind trial to compare lovastatin with placebo for prevention of first acute major coronary event in men and women without clinically evident atheroscler

20、otic CVD5,608 men and 997 women with average Total-C and LDL-C and below-average HDL-CDowns JR et al. JAMA 1998;279:16151622Air Force/Texas Coronary AtherAir Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)Changes in Lipid Parameters at 1 Year0.91.51.2-2.3-18.4-256-15-30-25-20-

21、15-10-50510TCLDL-CHDL-CTGPercent change from baselinePlaceboLovastatin*P value 0.001 for all lipid parameters: between group differences and changes on lovastatin from baseline to Year 1.Downs JR et al. JAMA 1998;279:16151622Copyright 1998, American Medical Association.Air Force/Texas Coronary Ather

22、No. at risk:LovastatinN = 3,304N = 3,270N = 3,228N = 3,184N = 3,134N = 1,688PlaceboN = 3,301N = 3,251N = 3,211N = 3,159N = 3,092N = 1,644Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)Primary End Point: First Acute Major Coronary Event0.070.060.050.040.030.020.010.00012345

23、5+Cumulative incidencePlaceboLovastatin37% risk reducation(P 60 y)Study duration: 7 yMedian follow-up: 5.1 yPrimary end point: nonfatal MI or coronary deathRubins HB et al. N Engl J Med 1999;341:410418Veterans Affairs High-Density Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Tr

24、ial (VA-HIT) Effects on Lipid Levels at 1 YearRubins HB et al. N Engl J Med 1999;341:410418LDL-CHDL-CTCTG% change with gemfibrozil versus placebo-35-30-25-20-15-10-50510No change+6-4-31Veterans Affairs High-Density Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT) Eff

25、ects of Fibrate on CVD Events in CHD Patients With Isolated Low HDL-C*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:Vetera

26、ns Affairs High-Density Bezafibrate Infarction Prevention Trial (BIP) Bezafibrate (400 mg/d) versus placebo 3,122 men and women with documented CHDMean age: 60 y (range: 4574 y) 78% with prior MIBaseline lipid parameters:TC 180250 mg/dL HDL-C 45 mg/dL LDL-C 180 mg/dL*TG 300 mg/dLPrimary end point: f

27、atal 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 Heart J 1998;19:H42H47Bezafibrate Infarction PreventBezafibrate Infarction Prevention Trial (BIP) Changes in Lipid Levels-4-512-22-25-20-15-10-5051015TC(212)L

28、DL-C(148)HDL-C(35)TG(149)Baseline (mg/dL):% change from baselinePresented at European Society of Cardiology Meeting, Vienna, 1998Bezafibrate Infarction PreventBezafibrate Infarction Prevention Trial (BIP)Effect on Primary End Point-9-40-45-40-35-30-25-20-15-10-50All patientsTG 200 mg/dLP = 0.27P = 0

29、.03Relative risk reduction (%)Presented at European Society of Cardiology Meeting, Vienna, 1998Bezafibrate Infarction PreventCoronary Drug ProjectLong-term efficacy and safety of five lipid-influencing drugsNiacin, clofibrate, dextrothyroxine, and two estrogen regimens8,341 men (aged 3064 y) with pr

30、evious MIInitial study conducted between 1966 and 1975 (mean follow-up: 6.2 y)At end of study, 6,008 survivors followed for additional mean 8.8 yCanner PL et al. J Am Coll Cardiol 1986;8:12451255Coronary Drug ProjectLong-termCoronary Drug Project Long-Term Mortality Benefit of Niacin in Post-MI Pati

31、entsNiacinPlaceboP = 0.00121009080706050403020100246810121416Years of follow-upSurvival (%)Canner PL et al. J Am Coll Cardiol 1986;8:12451255 Coronary Drug Project Long-TeHeart and Estrogen/Progestin Replacement Study (HERS)Randomized, double-blind, placebo-controlled trial to determine whether estr

32、ogens plus progestin alter risk of CHD events in postmenopausal women with coronary diseaseCEE (0.625 mg/d) plus MPA (2.5 mg/d) versus placebo2,763 postmenopausal women (mean age: 67 y) with coronary disease and intact uterus Average follow-up: 4.1 yPrimary end point: nonfatal MI or CHD deathCEE = c

33、onjugated equine estrogen; MPA = medroxyprogesterone acetateHulley S et al. JAMA 1998;280:605613Heart and Estrogen/Progestin RHeart and Estrogen/Progestin Replacement Study (HERS) Changes in Lipid Levels at 1 Year-20-15-10-5051015LDL-CHDL-CTGMean % change from baselinePlaceboEstrogen/progestin*P 0.0

34、01-3-14*-28*10*2Hulley S et al. JAMA 1998;280:605613.Copyright 1998, American Medical Association.Heart and Estrogen/Progestin RHeart and Estrogen/Progestin Replacement Study (HERS)Cumulative Incidence of Primary CHD Events1510500(2,763)1(2,631)2(2,506)3(2,392)4(1,435)5(113)Incidence (%)Follow-up, y (No