1、COOCCH3COOCHCH3CH3ClCH3OCCH3COOC2H5CH3ClCH3CH3OCH2CH2CH2CH2CH3COOHCH3CFenofibrateClofibrateGemfibrozil%ReductionHMG CoA RI20-50%Bile acid resins15-25%Dose dependentNicotinic acid15-30%Gemfibrozil10-15%Fixed doseFenofibrate10-25%HDL-CTriglycerideNicotinic acid10-25%20-50%Fibrates 10-25%20-50%HMG CoA
2、RI 5-10%10-25%Bile acid resins3-5%0-20%Indications: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
3、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,BIPGoldberg AC,et al.
4、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-cholesterol9
5、2.1 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 24.6-44.10.001Goldberg AC,et al.Clin Ther.1989;11:69-83.*These are mean percentage changes,not percentage chang
6、es 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.
7、0 19.9-54.50.0001VLDL-triglyceride543.3 50.8204.7 23.0-50.60.0001Goldberg AC,et al.Clin Ther.1989;11:69-83.nMany 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 choles
8、terol-depleted LDL.nWhen triglycerides are reduced with therapy,the composition of LDL normalizes.This can elevate LDL-C levels.Brown 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
9、 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+8.4(Randomized,Crossover Study)Farnier M,et al.Arch Int
10、 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 Months-28-28-34-36-37-50-40-30-20-100Total-CLDL-CHDL-CTrigFenofibrateSimvastatinFarnier M,et al.Arch Int Med.1994;1
11、54:441-449.(Type IIa)%Change from BaselineNCNC=no changeNCNC-23-21-25-302917-5218-60-45-30-150153045Total-CLDL-CHDL-CTrigFenofibrateSimvastatinFarnier M,et al.Arch Int Med.1994;154:441-449.(Type IIb)%Change from BaselinenLipoprotein and Coronary Atherosclerosis Study(LCAS)nPost Coronary Artery Bypas
12、s Graft Trial(Post-CABG)nBezafibrate Coronary Atherosclerosis Intervention Trial(BECAIT)nLopid Coronary Angiography Trial(LOCAT)Hypothesis: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,T
13、G 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.Habits/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
14、Med 1999;341:410-418.Rubins 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 years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
