贝特类药物在血脂治疗中的作用PPT课件.ppt
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349.8
GVoLldDbLe-trrgigAlyCc,eeritdael. Clin The±r. 19348.93;11:69-18737..8 ± 24.6
Percent Change*
-9.1 -44.7
NS +19.6
-46.2
-44.1
P
<0.001 <0.001
0.8570 0.0014
33.7 ± 1.1
136.7 ± 5.3 40.3 ± 1.9
432.0 *TTohetsaelatrreigmleyancpeerricdenetage changes, no±t perce1n9ta.g1e changes in2m2e3an.4s. ± 13.9
NS=Not statistically significant when compared to placebo (12% increase).
*These are mean percentage changes, not percentage changes in means.
Goldberg AC, et al. Clin Ther. 1989;11:69-83.
Fenofibrate for the Treatment of Type IV and V Hyperlipoproteinemias
O
CH3
CH3
Cl
C
O C COO CH
CH3
CH3
Fenofibrate
CH3
Cl
O C COOC2H5
Clofibrate
CH3
CH3
CH3
O CH2 CH2 CH2 CH2 C COOH
CH3
Gemfs on LDL-C Levels
HMG CoA RI Bile acid resins Nicotinic acid
Fenofibrate
After (mean ± SE)
223.3 ±6.6 53.7 ±3.4 131.0 ±6.0 36.0 ±1.8 308.0 ±19.9 204.7 ±23.0
Percent Changes*
-13.8 -49.4 +45.0 +22.9 -54.5 -50.6
P
0.0001 0.0001 0.0002 0.0029 0.0001 0.0001
Total cholesterol VLDL-cholesterol LDL-cholesterol HDL-cholesterol Total triglyceride VLDL-triglyceride
Before (mean ± SE)
261.0 ±6.7 126.2 ±7.0 103.1 ±6.8 29.6 ±1.3 725.6 ±37.4 543.3 ±50.8
Side Effects: GI upset (8%), cholelithiasis, myositis, abn LFTs
Contraindications: Hepatic or renal dysfunction Pre-existing gallbladder disease
Intervention Trials: Helsinki Heart Study, LOCAT, BECAIT, VA-HIT, BIP
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.
Mechanism of Action: Increases peripheral lipolysis and decreases hepatic TG production
Efficacy: Decreases TG 25-50% LDL decreases, remains the same or increases Increases HDL 15-25% in hypertriglyceridemia
HDL-C
10-25% 10-25% 5-10% 3-5%
Triglyceride
20-50% 20-50% 10-25% 0-20%
Fibric Acid Derivatives
Indications: Adjunctive therapy to diet Hypertriglyceridemia (Type IV and V) Combined hyperlipidemia (Type IIb) with low HDL who do not respond to NA
Before (mean ± SE)
After ( mean ± SE)
Total cholesterol VLDL-cholesterol
251.8 ± 5.3
92.1 ± 6.8
227.4 ± 6.7 45.8 ± 4.5
LDL-cholesterol HDL-cholesterol
128.4 ± 7.1
Fenofibrate for the Treatment of Type IV and V Hyperlipoproteinemias
A Double-Blind, Placebo-Controlled Multicenter US Study
Fenofibrate
Group A (350-499 mg/dL)
Gemfibrozil Fenofibrate
20-50% 15-25% 15-30%
% Reduction Dose dependent
10-15% 10-25%
Fixed dose
Effect of Drugs on Triglyceride and HDL-C Levels
Nicotinic acid Fibrates HMG CoA RI Bile acid resins
<0.001
<0.001
Fenofibrate for the Treatment of Type IV and V Hyperlipoproteinemias
A Double-Blind, Placebo-Controlled Multicenter US Study
Group B (500-1500 mg/dL)
GVoLldDbLe-trrgigAlyCc,eeritdael. Clin The±r. 19348.93;11:69-18737..8 ± 24.6
Percent Change*
-9.1 -44.7
NS +19.6
-46.2
-44.1
P
<0.001 <0.001
0.8570 0.0014
33.7 ± 1.1
136.7 ± 5.3 40.3 ± 1.9
432.0 *TTohetsaelatrreigmleyancpeerricdenetage changes, no±t perce1n9ta.g1e changes in2m2e3an.4s. ± 13.9
NS=Not statistically significant when compared to placebo (12% increase).
*These are mean percentage changes, not percentage changes in means.
Goldberg AC, et al. Clin Ther. 1989;11:69-83.
Fenofibrate for the Treatment of Type IV and V Hyperlipoproteinemias
O
CH3
CH3
Cl
C
O C COO CH
CH3
CH3
Fenofibrate
CH3
Cl
O C COOC2H5
Clofibrate
CH3
CH3
CH3
O CH2 CH2 CH2 CH2 C COOH
CH3
Gemfs on LDL-C Levels
HMG CoA RI Bile acid resins Nicotinic acid
Fenofibrate
After (mean ± SE)
223.3 ±6.6 53.7 ±3.4 131.0 ±6.0 36.0 ±1.8 308.0 ±19.9 204.7 ±23.0
Percent Changes*
-13.8 -49.4 +45.0 +22.9 -54.5 -50.6
P
0.0001 0.0001 0.0002 0.0029 0.0001 0.0001
Total cholesterol VLDL-cholesterol LDL-cholesterol HDL-cholesterol Total triglyceride VLDL-triglyceride
Before (mean ± SE)
261.0 ±6.7 126.2 ±7.0 103.1 ±6.8 29.6 ±1.3 725.6 ±37.4 543.3 ±50.8
Side Effects: GI upset (8%), cholelithiasis, myositis, abn LFTs
Contraindications: Hepatic or renal dysfunction Pre-existing gallbladder disease
Intervention Trials: Helsinki Heart Study, LOCAT, BECAIT, VA-HIT, BIP
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.
Mechanism of Action: Increases peripheral lipolysis and decreases hepatic TG production
Efficacy: Decreases TG 25-50% LDL decreases, remains the same or increases Increases HDL 15-25% in hypertriglyceridemia
HDL-C
10-25% 10-25% 5-10% 3-5%
Triglyceride
20-50% 20-50% 10-25% 0-20%
Fibric Acid Derivatives
Indications: Adjunctive therapy to diet Hypertriglyceridemia (Type IV and V) Combined hyperlipidemia (Type IIb) with low HDL who do not respond to NA
Before (mean ± SE)
After ( mean ± SE)
Total cholesterol VLDL-cholesterol
251.8 ± 5.3
92.1 ± 6.8
227.4 ± 6.7 45.8 ± 4.5
LDL-cholesterol HDL-cholesterol
128.4 ± 7.1
Fenofibrate for the Treatment of Type IV and V Hyperlipoproteinemias
A Double-Blind, Placebo-Controlled Multicenter US Study
Fenofibrate
Group A (350-499 mg/dL)
Gemfibrozil Fenofibrate
20-50% 15-25% 15-30%
% Reduction Dose dependent
10-15% 10-25%
Fixed dose
Effect of Drugs on Triglyceride and HDL-C Levels
Nicotinic acid Fibrates HMG CoA RI Bile acid resins
<0.001
<0.001
Fenofibrate for the Treatment of Type IV and V Hyperlipoproteinemias
A Double-Blind, Placebo-Controlled Multicenter US Study
Group B (500-1500 mg/dL)