HDL和LDL风险评估与治疗优选课件

1、The Pyramid of Recent TrialsRelative Size of the Various Segments of the Population4SCAREWOSCOPSAFCAPS/TexCAPSLIPIDVery high cholesterol with CHD or MIModerately high cholesterol in high risk CHD or MINormal cholesterol with CHD or MIHigh cholesterol without CHD or MINo history of CHD or MIThe Pyram

2、id of Recent TrialsRAir Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) (1998)Evaluated the effects of lovastatin on first acute major coronary event in 6605 men and women without any coronary or vascular disease and withTC 180-254 mg/dlHDL-C 45 mg/dl in men and 47 mg/dl in wo

3、menLDL-C 130-190 mg/dl, or LDL-C 125-129 mg/dl with TC/HDL-C ratio 6Randomized to lovastatin 20 mg vs. placebo with titration to 40 mg with goal of LDL-C 110 mg/dlMean follow-up 5 yearsDowns JR et al. JAMA 1998;279:1615-1622.Air Force/Texas Coronary AtherAFCAPS/TexCAPS Results37%40%1st acute major c

4、oronary eventp0.001Fatal or nonfatal MIp=0.002Risk Reduction with Rx15011525% reductionDowns JR et al. JAMA 1998;279:1615-1622.AFCAPS/TexCAPS Results37%40%AFCAPS/TexCAPS Tertiary Endpoint Analysis: Mortality*Too few for survival analysesAFCAPS/TexCAPS Tertiary EndpoiNCEP Adult Treatment Panel II Gui

5、delinesNational Cholesterol Education Program Circulation 1994;89:13291445.NCEP Adult Treatment Panel II PravastatinPravastatinPravastatinPlaceboPlaceboPlaceboCARE: Is There a Lower Threshold?Sacks FM et al. N Engl J Med. 1996;335:1001-1009.Copyright 1996 Massachusetts Medical Society. All rights re

6、served.LDL-C 150 mg/dlChange in risk +3%p=0.85Change in risk 35%p=0.008Change in risk 26%p0.001Incidence (%)YearsYearsYears201553035251002015530352510020155303525100132450132450132450PravastatinPravastatinPravastaOn-Treatment LDL Levels and Correlation with Major Coronary Events in 4SAbsolute differ

7、ence in event rate:2.3%5.6%Circulation 1997;96:I-717On-Treatment LDL Levels and CoPitt B et al. N Engl J Med 1999;341:70-76.CAD 1 lesion 50% stenosisLDL-C 115 mg/dL (3.0 mmol/L)LVEF 40%Bruce protocol treadmill test or 20-W/minbicycle exercise test 4 minAtorvastatin 80 mg/d+usual medical therapyn=164

8、*Angioplasty+usual care, including lipid loweringn=17718 monthsOccurrence of ischemic events (death from cardiac causes, resuscitation after cardiac arrest, nonfatal MI, CVA, CABG, angioplasty, worsening angina verified by objective evidence resulting in hospitalization)Time to first ischemic eventS

9、afety*1 patient did not receive atorvastatin.11 patients did not have baseline revascularization. AVERT: Study DesignPitt B et al. N Engl J Med 1990510152025AtorvastatinAngioplasty/UC% of patientswith anischemic event13%21%36% difference*(p = 0.048)2237*p=0.048 vs an adjusted significance level of p

10、=0.045.Pitt B et al. N Engl J Med 1999;341:70-76.Results - Intent to Treat0510152025AtorvastatinAngiopla05101520250.00.51.01.5p=0.027Risk reduction 36%(95% CI: 5% to 67%)Cumulative Incidence (%)AtorvastatinAngioplasty/UCTime since randomization (yr)Pitt B et al. N Engl J Med 1999;341:70-76.Copyright

11、 1999 Massachusetts Medical Society. All rights reserved.Time to First Ischemic Event:Intent-to-Treat Analysis05101520250.00.51.01.5p=0.027C*Significantly different from angioplasty/UC (p0.05). To convert TG to mmol/L, multiply by 0.011.Note: 73% of angioplasty/UC-treated patients were on lipid-lowe

12、ring medication.18% 31% *46% *10% 10% 11% *8% 11% 250(6.5)200(5.2)150(3.9)100(2.6)50(1.3)0LDL-CTCTGHDL-Cmg/dL(mmol/L)Atorvastatin baselineAtorvastatin end of studyAngioplasty/UC baselineAngioplasty/UC end of studyPitt B et al. N Engl J Med 1999;341:70-76.Copyright 1999 Massachusetts Medical Society.

13、 All rights reserved.Summary of Lipid Parameters*Significantly different from Ballantyne CM. Am J Cardiol. 1998;82:3Q-12Q.Reprinted with permission from Excerpta Medica Inc.2 prevention placebo2 prevention statin1 prevention placebo1 prevention statinAFCAPSAFCAPSWOSCOPSWOSCOPSCARECARELIPIDLIPID4S4SE

14、vent Rate (%)Clinical Event Rates by LDL-C Achieved in Statin TrialsBallantyne CM. Am J Cardiol. 1How Low Should You Go?SEARCH: Study of the Effectiveness of Additional Reductions of Cholesterol and HomocysteineSimvastatin 20 mg vs. 80 mgTNT: Treating to New TargetsAtorvastatin 10 mg vs. 80 mgHow Lo

15、w Should You Go?SEARCH: Clinical JudgmentThe NCEP ATP II guidelines recommend the use of clinical judgment in deciding whether to initiate drug therapy inPatients with CHD and LDL-C 100129 mg/dlPatients without CHD who have 2 risk factors and LDL-C 130159 mg/dlMiddle-aged and older patients without

16、CHD who have 2 risk factors and LDL-C 160189 mg/dlNational Cholesterol Education Program Circulation 1994;89:13291445.Clinical JudgmentThe NCEP ATP 2 RF2 RFCHDNumber of US Adults (millions)NHANES III Adult Population Estimatesby ATP II Risk CategoryJacobson TA et al. Arch Intern Med. 200

17、0;160(9):1361-9.2 RF2 RFCHDNumber of US AdulLDL-C (mg/dl)Number of US Adults (millions) without CHD and with 2 RF606069707980899099100109110119120129130139140149150159160169170179180189190199200209210219220229230239240249250259260269270279280289290299300309310319320329330339340349350with CHDLDL-C Di

18、stribution in U.S. Adults Data from NHANES III, 19881994Jacobson TA et al. Arch Intern Med. 2000;160(9):1361-9.LDL-C (mg/dl)Number of US AdulUS Adults Requiring Drug Therapy Assuming 10% LDL-C Reduction with Diet2 RF2 RFCHDTotalNumber of US Adults (millions)10.428.4Jacobson TA et

19、al. Arch Intern Med. 2000;160(9):1361-9.US Adults Requiring Drug TheraEffect of Statin Therapy on CHD: Clinical Events TrialsJacobson TA et al. Arch Intern Med 1998;158:19771989.*Nonfatal MI or CHD death in WOSCOPS, CARE, LIPID; nonfatal or fatal MI, unstable angina, or sudden cardiac death as first

20、 event in AFCAPS; nonfatal MI, coronary death, or resuscitated cardiac arrest in 4S.vs. placeboEffect of Statin Therapy on CHLDL and HDL Impact on CHD RiskA Compounded Rather Than Additive Impact 010020030040055195HDL-cholesterol (mg/dL)LDL-cholesterol (mg/dL)Incidence per1000 (in 6 years)Assmann G,

21、 et al. Atherosclerosis 1996;124(suppl):S11-S20.Reprinted with permission from Elsevier Science.LDL and HDL Impact on CHD RiskHDL is a major factor in predicting CAD02040608010012055HDL-cholesterol (mg/dL)Incidence of CHD (per 1000 in 6 years)n=4,407Assmann G, et al. Atherosclerosis 1996;124(suppl):

22、S11-S20.Reprinted with permission from Elsevier Science.HDL is a major factor in prediHDL-C Distribution in US AdultsData from NHANES III, 19881994.Number of US Adults (millions)HDL-C (mg/dl)HDL-C Distribution in US AdultHDL-C in Clinical PracticeRisk assessmentRoutinely measured in all adult patien

23、tsHDL-C 35 mg/dL is a major positive risk factorHDL-C 60 mg/dL is a negative risk factor; subtract 1 risk factor from totalRisk reductionNonpharmacologic therapy (exercise, weight loss, smoking cessation)Pharmacologic therapyClinical trial data show decreased CAD progression and decreased CAD events

24、 with increased HDL-CHDL-C in Clinical PracticeRiskProgression (MLD decrease), mmHDL-C 35 mg/dl(p=0.0004)n=43n=25HDL-C 35 mg/dl(p=0.09)n=128n=1430.0650.2740.0360.083p=0.01Ballantyne CM et al. Circulation 1999;99:736-743.Reduction in CAD Progression with Fluvastatin in Low vs. High HDL-C PatientsProg

25、ression (MLD decrease), mmBallantyne CM et al. Circulation 1999;99:736-743.FluvastatinPlaceboHDL-C 35 mg/dlp=0.002FluvastatinHDL-C 35 mg/dlp=0.232122.501.000.750.500.250.001.000.750.500.250.00Probability of event-free survivalYearsPlaceboReduced CAD Events with Fluvastatin in Low HDL-C Patients122.5

26、0Ballantyne CM et al. CirculatiAngiographic Trials in LowHDL-C PatientsBallantyne CM et al. Circulation 1999;99:736-743.Baseline (mg/dl)%MLDPL MLDDR (mm)TrialDrugLDL-CHDL-CLDL-CHDL-CLCASfluvastatin 40 mg/d1464325+90.07LCAS HDL-C 35 mg/dlfluvastatin 40 mg/d1433225+160.21BECAITbezafibrate 600 mg/d1803

27、43.5+90.11LOCATgemfibrozil 1200 mg/d138314.5+210.04Angiographic Trials in LowHDLAtherosclerosis Progression and Baseline HDL-C:Results from Post-CABGProgression rate (%)HDL-C (mg/dl)Moderatetherapy(LDL-C 134)Aggressivetherapy(LDL-C 95) Relative risk 95% CI3547300.480.350.67353940280.580.390.85404437

28、250.560.350.894530270.870.571.33Hunninghake D et al. Circulation 1997;96:I-413.Atherosclerosis Progression anAdapted from Ballantyne CM et al. Circulation 1999;99:736-743.4SWOSCOPSAFCAPSCoronary Events (%)40345238 4343LIPID 39 130 mg/dL (mean 156)- Triglycerides 300-700 mg/dL (median 389)Treatment:

29、placebo, simvastatin 40 and 80 mg/day (6 weeks each)Main endpoints:- TC, TG, apo B, LDL-C, VLDL-C, apo A-I, HDL-CHunninghake DB et al. J Am Coll Cardiol 1999;33:244ASimvastatin Combined HyperlipiChanges in LipidsHunninghake DB et al. J Am Coll Cardiol 1999;33:244A-29-2813-36-3316-40-30-20-1001020Sim

30、vastatin 40 mg/dSimvastatin 80 mg/dLDL-CTGMean % ChangeHDL-Cp0.001p0.001p0.001Changes in LipidsHunninghake DComparison of Simvastatin and AtorvastatinStudy Objective:To compare relative efficacy of simvastatin and atorvastatinStudy Design:12-week, open-label, randomized, parallel-group, multicenter

31、study 842 patients, men and women, ages 21-70Following a 4-week diet run-in period, patients were randomized into 4 treatment groups (simvastatin 40 mg, simvastatin 80 mg, atorvastatin 20 mg, atorvastatin 40 mg) for 12 weeksCrouse JR III et al. Am J Cardiol 1999;83:1476-1477.Comparison of Simvastati

32、n and Lipid ChangesCrouse JR III et al. Am J Cardiol 1999;83:1476-1477.-60-50-40-30-20-10010Simvastatin 40 mg/dAtorvastatin 20 mg/dSimvastatin 80 mg/dAtorvastatin 40 mg/dLDL-CHDL-CTGapo A-I-43-45-49-51-23-23-25-30+7+4+7+3+5+6+60Mean % Changep0.05p0.05p0.05p0.01p0.01p0.001Lipid ChangesCrouse JR III e

33、t Subgroup Analysis for HDL-C above or below 35 mg/dlMean % change in HDL-0.005p0.05Crouse JR III et al. Am J Cardiol 1999;83:1476-1477.Reprinted with permission from Excerpta Medica, Inc.Subgroup Analysis for HDL-C aCombination Therapy: Statin + Nicotinic AcidSimvastatin 10 mg/day + ni

34、cotinic acid titrated up to 1.5 g/day1LDL-C by 29%HDL-C by 31%TG by 31%Fluvastatin 20 mg/day + nicotinic acid titrated up to 3 g/day2LDL-C by 40%HDL-C by 28%TG by 30%1Stein EA et al. J Cardiovasc Pharmacol Ther 1996;1:107-116.2Jacobson TA et al. Am J Cardiol 1994;74:149-154.Combination Therapy: Statin + Combination Therapy: Statin + FibrateLovastatin 2040 mg/day + gemfibrozil 1200 mg/day1LDL-C by 26%HDL-C by 3%TG by 35%Pravastatin 40 mg/day + gemfibrozil 1200 mg/day2LDL-C by 37%HDL-C by 17%TG by 42%1Glueck CJ et al