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COOCCH3COOCHCH3CH3ClCH3OCCH3COOC2H5CH3ClCH3CH3OCH2CH2CH2CH2CH3COOHCH3CFenofibrateClofibrateGemfibrozilCOOCCH3COOCHCH3CH3ClCH3OCCH3CO%ReductionHMG CoA RI20-50%Bile acid resins15-25%Dose dependentNicotinic acid15-30%Gemfibrozil10-15%Fixed doseFenofibrate10-25%Effect of Drugs on LDL-C LevelsEffect of Drugs on LDL-C Levels%ReductionHMG CoA RI20-50%BilEffect of Drugs on Triglyceride Effect of Drugs on Triglyceride and HDL-C Levelsand HDL-C LevelsHDL-CTriglycerideNicotinic acid10-25%20-50%Fibrates 10-25%20-50%HMG CoA RI 5-10%10-25%Bile acid resins3-5%0-20%Effect of Drugs on TriglyceridFibric Acid DerivativesFibric Acid DerivativesIndications:Adjunctive therapy to dietHypertriglyceridemia(Type IV and V)Combined hyperlipidemia(Type IIb)with low HDL who do not respond to NAMechanism of Action:Increases peripheral lipolysis and decreases hepatic TG productionEfficacy:Decreases TG 25-50%LDL decreases,remains the same or increasesIncreases HDL 15-25%in hypertriglyceridemiaSide Effects:GI upset(8%),cholelithiasis,myositis,abn LFTsContraindications:Hepatic or renal dysfunctionPre-existing gallbladder diseaseIntervention Trials:Helsinki Heart Study,LOCAT,BECAIT,VA-HIT,BIPFibric Acid DerivativesIndicatGoldberg AC,et al.Clin Ther.1989;11:69-83.*These are mean percentage changes,not percentage changes in means.NS=Not statistically significant when compared to placebo(12%increase).FenofibrateGroup A(350-499 mg/dL)Before(mean SE)After(mean SE)PercentChange*PTotal cholesterol251.8 5.3227.4 6.7-9.10.001VLDL-cholesterol92.1 6.845.8 4.5-44.70.001LDL-cholesterol128.4 7.1136.7 5.3NS0.8570HDL-cholesterol33.7 1.140.3 1.9+19.60.0014Total triglyceride432.0 19.1223.4 13.9-46.20.001VLDL-triglyceride349.8 34.3177.8 24.6-44.10.001Fenofibrate for the Treatment of Fenofibrate for the Treatment of Type IV and V HyperlipoproteinemiasType IV and V HyperlipoproteinemiasA Double-Blind,Placebo-Controlled Multicenter US StudyA Double-Blind,Placebo-Controlled Multicenter US StudyGoldberg AC,et al.Clin Ther.Fenofibrate for the Treatment of Fenofibrate for the Treatment of Type IV and V HyperlipoproteinemiasType IV and V HyperlipoproteinemiasA Double-Blind,Placebo-Controlled Multicenter US StudyA Double-Blind,Placebo-Controlled Multicenter US StudyGoldberg AC,et al.Clin Ther.1989;11:69-83.*These are mean percentage changes,not percentage changes in means.FenofibrateGroup B(500-1500 mg/dL)Before(mean SE)After(mean SE)Percent Changes*PTotal cholesterol261.0 6.7223.3 6.6-13.80.0001VLDL-cholesterol126.2 7.053.7 3.4-49.40.0001LDL-cholesterol103.1 6.8131.0 6.0+45.00.0002HDL-cholesterol29.6 1.336.0 1.8+22.90.0029Total triglyceride725.6 37.4308.0 19.9-54.50.0001VLDL-triglyceride543.3 50.8204.7 23.0-50.60.0001Fenofibrate for the TreatmentGoldberg AC,et al.Clin Ther.1989;11:69-83.Fenofibrate for the Treatment of Fenofibrate for the Treatment of Type IV and V HyperlipoproteinemiasType IV and V HyperlipoproteinemiasA Double-Blind,Placebo-Controlled Multicenter US StudyA Double-Blind,Placebo-Controlled Multicenter US StudynMany patients with markedly elevated triglycerides have reduced LDL-C levels because of a derangement in the normal composition of LDL.nThis derangement produces a triglyceride-rich and cholesterol-depleted LDL.nWhen triglycerides are reduced with therapy,the composition of LDL normalizes.This can elevate LDL-C levels.Goldberg AC,et al.Clin Ther.Effects of Fenofibrate on Plasma LipidsEffects of Fenofibrate on Plasma LipidsDouble-Blind,Multicenter Study in Patients Double-Blind,Multicenter Study in Patients with Type IIa or IIb Hyperlipidemiawith Type IIa or IIb HyperlipidemiaBrown WV,et al.Arteriosclerosis.1986;6:670-678.p0.10Percentage Changes at Endpoint from Baseline Values after 24 Weeks of Double Blind Study vs.Placebo(Plb)Type IIa (%)Type IIb (%)Fenon=92Plbn=88Fenon=24Plb n=22Total Cholesterol-17.5-0.4-15.8+4.6LDL Cholesterol-20.3+0.4-6.1-0.5HDL Cholesterol+11.1-1.2+15.3-3.5Total Triglycerides-37.9-4.2-44.6+22.3LDL/HDL Cholesterol-27.1-1.9-13.3 0.0VLDL Cholesterol-38.4-2.5-52.7+8.4Effects of Fenofibrate on Plas(Randomized,Crossover Study)Farnier M,et al.Arch Int Med.1994;154:441-449.Fenofibrate200 mg/daySimvastatin20 mg/daySimvastatin20 mg/dayFenofibrate200 mg/dayType IIa,n=16Type IIb,n=14Type IIa,n=16Type IIb,n=14Group 1Group 2IIII I I I03 6 MonthsComparative Efficacy and Safety of Micronized Fenofibrate Comparative Efficacy and Safety of Micronized Fenofibrate and Simvastatin in Patients with Primary Type IIa or IIb and Simvastatin in Patients with Primary Type IIa or IIb HyperlipidemiaHyperlipidemia(Randomized,Crossover Study)FFenofibrate vs.SimvastatinFenofibrate vs.SimvastatinEffect on Overall Lipid ProfileEffect on Overall Lipid ProfileFarnier M,et al.Arch Int Med.1994;154:441-449.(Type IIa)%Change from BaselineNCNC=no changeNCNCFenofibrate vs.SimvastatinEfFenofibrate vs.SimvastatinFenofibrate vs.SimvastatinEffect on Overall Lipid ProfileEffect on Overall Lipid ProfileFarnier M,et al.Arch Int Med.1994;154:441-449.(Type IIb)%Change from BaselineFenofibrate vs.SimvastatinEfAngiographic Studies inAngiographic Studies inLowHDL-C SubjectsLowHDL-C SubjectsnLipoprotein and Coronary Atherosclerosis Study(LCAS)nPost Coronary Artery Bypass Graft Trial(Post-CABG)nBezafibrate Coronary Atherosclerosis Intervention Trial(BECAIT)nLopid Coronary Angiography Trial(LOCAT)Angiographic Studies inLowHDVA-HIT:DesignVA-HIT:DesignHypothesis:Gemfibrozil treatment of“isolated”low HDL-C will 2 CHD events.Subjects:n2531 male veterans 74 year(avg 64)n2 prevention(MI,revasc,angina,+angio)nHDL 40,LDL 140,TG 300 mg/dLTreatment:gemfibrozil 600 mg bidEndpoints:nonfatal MI,CHD deathFollow-up:5.1 yearsRubins HB et al.N Engl J Med 1999;341:410-418.VA-HIT:DesignHypothesis:GemVA-HIT:Baseline DataVA-HIT:Baseline DataHabits/MedsCigarettes21%DM(Hx)25%ASA82%blocker43%ACEI21%DemographicsBMI 29+5WHR 0.96+0.05LipidsHDL-C 32 mg/dlLDL-C 111 mg/dlTG 161 mg/dlRubins HB et al.N Engl J Med 1999;341:410-418.VA-HIT:Baseline DataHabits/MeVA-HIT:ResultsVA-HIT:ResultsRubins HB et al.N Engl J Med 1999;341:410-418.ParameterPlacRx%PHDL-C 32 34 6%.001LDL-C113113 0%NSTG16611531%.001NFMI/CHD275219 22%.006Stroke(confirmed)76 58 25%.11+stroke330258 24%2.0)-Concomitant medications:Itraconazole,Ketoconazole Cyclosporin AErythromycin-Age 70 yearsStatin plus Fibrate Combinatio演讲完毕，谢谢观看！Thank you for reading!In order to facilitate learning and use,the content of this document can be modified,adjusted and printed at will after downloading.Welcome to download!汇报人：XXX汇报日期：20XX年10月10日演讲完毕，谢谢观看！Thank you for readin
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