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Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,C,O,O,C,CH,3,COO,CH,CH,3,CH,3,Cl,CH,3,O,C,CH,3,COOC,2,H,5,CH,3,Cl,CH,3,CH,3,O,CH,2,CH,2,CH,2,CH,2,CH,3,COOH,CH,3,C,Fenofibrate,Clofibrate,Gemfibrozil,COOCCH3COOCHCH3CH3ClCH3OCCH3CO,%Reduction,HMG CoA RI,20-50%,Bile acid resins,15-25%,Dose dependent,Nicotinic acid,15-30%,Gemfibrozil,10-15%,Fixed dose,Fenofibrate,10-25%,Effect of Drugs on LDL-C Levels,%ReductionHMG CoA RI20-50%Bil,Effect of Drugs on Triglyceride and HDL-C Levels,HDL-C,Triglyceride,Nicotinic acid,10-25%,20-50%,Fibrates,10-25%,20-50%,HMG CoA RI,5-10%,10-25%,Bile acid resins,3-5%,0-20%,Effect of Drugs on Triglycerid,Fibric Acid Derivatives,Indications:,Adjunctive therapy to dietHypertriglyceridemia(Type IV and V)Combined hyperlipidemia(Type IIb)with low HDL who do not respond to NA,Mechanism of Action:,Increases peripheral lipolysis and decreases hepatic TG production,Efficacy:,Decreases TG 25-50%LDL decreases,remains the same or increasesIncreases HDL 15-25%in hypertriglyceridemia,Side Effects:,GI upset(8%),cholelithiasis,myositis,abn LFTs,Contraindications:,Hepatic or renal dysfunctionPre-existing gallbladder disease,Intervention Trials:,Helsinki Heart Study,LOCAT,BECAIT,VA-HIT,BIP,Fibric Acid DerivativesIndicat,Goldberg 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).,Fenofibrate,Group A,(350-499 mg/dL),Before,(mean SE),After,(mean SE),Percent,Change*,P,Total cholesterol,251.8,5.3,227.4,6.7,-9.1,0.001,VLDL-cholesterol,92.1,6.8,45.8,4.5,-44.7,0.001,LDL-cholesterol,128.4,7.1,136.7,5.3,NS,0.8570,HDL-cholesterol,33.7,1.1,40.3,1.9,+19.6,0.0014,Total triglyceride,432.0,19.1,223.4,13.9,-46.2,0.001,VLDL-triglyceride,349.8,34.3,177.8,24.6,-44.1,0.001,Fenofibrate for the Treatment of Type IV and V Hyperlipoproteinemias,A Double-Blind,Placebo-Controlled Multicenter US Study,Goldberg AC,et al.Clin Ther.,Fenofibrate for the Treatment of Type IV and V Hyperlipoproteinemias,A Double-Blind,Placebo-Controlled Multicenter US Study,Goldberg AC,et al.,Clin Ther,.1989;11:69-83.,*,These are mean percentage changes,not percentage changes in means.,Fenofibrate,Group B,(500-1500 mg/dL),Before,(mean SE),After,(mean SE),Percent Changes*,P,Total cholesterol,261.0,6.7,223.3,6.6,-13.8,0.0001,VLDL-cholesterol,126.2,7.0,53.7,3.4,-49.4,0.0001,LDL-cholesterol,103.1,6.8,131.0,6.0,+45.0,0.0002,HDL-cholesterol,29.6,1.3,36.0,1.8,+22.9,0.0029,Total triglyceride,725.6,37.4,308.0,19.9,-54.5,0.0001,VLDL-triglyceride,543.3,50.8,204.7,23.0,-50.6,0.0001,Fenofibrate for the Treatment,Goldberg AC,et al.,Clin Ther,.1989;11:69-83.,Fenofibrate for the Treatment of Type IV and V Hyperlipoproteinemias,A Double-Blind,Placebo-Controlled Multicenter US Study,Many patients with markedly elevated triglycerides have reduced LDL-C levels because of a derangement in the normal composition of LDL.,This derangement produces a triglyceride-rich and cholesterol-depleted LDL.,When 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 Lipids,Double-Blind,Multicenter Study in Patients with Type IIa or IIb Hyperlipidemia,Brown WV,et al.,Arteriosclerosis,.1986;6:670-678.,p0.10,Percentage Changes at Endpoint from Baseline Values after 24 Weeks of Double Blind Study vs.Placebo(Plb),Type IIa (%),Type IIb (%),Feno,n=92,Plb,n=88,Feno,n=24,Plb,n=22,Total Cholesterol,-17.5,-0.4,-15.8,+4.6,LDL Cholesterol,-20.3,+0.4,-6.1,-0.5,HDL Cholesterol,+11.1,-1.2,+15.3,-3.5,Total Triglycerides,-37.9,-4.2,-44.6,+22.3,LDL/HDL Cholesterol,-27.1,-1.9,-13.3,0.0,VLDL Cholesterol,-38.4,-2.5,-52.7,+8.4,Effects of Fenofibrate on Plas,(Randomized,Crossover Study),Farnier M,et al.,Arch Int Med.,1994;154:441-449.,Fenofibrate,200 mg/day,Simvastatin,20 mg/day,Simvastatin,20 mg/day,Fenofibrate,200 mg/day,Type IIa,n=16,Type IIb,n=14,Type IIa,n=16,Type IIb,n=14,Group 1,Group 2,IIII I I I,03 6,Months,Comparative Efficacy and Safety of Micronized Fenofibrate and Simvastatin in Patients with Primary Type IIa or IIb Hyperlipidemia,(Randomized,Crossover Study)F,Fenofibrate vs.SimvastatinEffect on Overall Lipid Profile,Farnier M,et al.,Arch Int Med.,1994;154:441-449.,(Type IIa),%Change from Baseline,NC,NC=no change,NC,NC,Fenofibrate vs.SimvastatinEf,Fenofibrate vs.SimvastatinEffect on Overall Lipid Profile,Farnier M,et al.,Arch Int Med.,1994;154:441-449.,(Type IIb),%Change from Baseline,Fenofibrate vs.SimvastatinEf,Angiographic Studies inLowHDL-C Subjects,Lipoprotein and Coronary Atherosclerosis Study(LCAS),Post Coronary Artery Bypass Graft Trial(Post-CABG),Bezafibrate Coronary Atherosclerosis Intervention Trial(BECAIT),Lopid Coronary Angiography Trial(LOCAT),Angiographic Studies inLowHD,VA-HIT:Design,Hypothesis:,Gemfibrozil treatment of“isolated”low HDL-C will,2 CHD events.,Subjects:,2531 male veteran
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