贝特类药物在血脂治疗中的作用
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Fenofibrate
Clofibrate
Gemfibrozil
Effect of Drugs on LDL-C Levels
Effect of Drugs on Triglyceride and HDL-C Levels
Fibric Acid Derivatives
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 for the Treatment of Type IV and V Hyperlipoproteinemias A Double-Blind, Placebo-Controlled Multicenter US Study
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.
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.
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.
p<0.01 except for LDL-C in Type IIb, where p>0.10
(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
I I I I I I I
0 3 6
Months
Comparative Efficacy and Safety of Micronized Fenofibrate and Simvastatin in Patients with Primary Type IIa or IIb Hyperlipidemia
Fenofibrate vs. Simvastatin Effect 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. Simvastatin Effect on Overall Lipid Profile
Farnier M, et al. Arch Int Med. 1994;154:441-449.
(Type IIb)
% Change from Baseline
Angiographic Studies in Low–HDL-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)
VA-HIT: Design
Hypothesis: Gemfibrozil treatment of “isolated” low HDL-C will ? 2o CHD events.
Subjects:
2531 male veterans < 74 year (avg 64)
2o prevention (MI, revasc, angina, + angio)
HDL ? 40, LDL ? 140, TG ? 300 mg/dL
Treatment: gemfibrozil 600 mg bid
Endpoints: nonfatal MI, CHD death
Follow-up: 5.1 years
Rubins HB et al. N Engl J Med 1999;341:410-418.
VA-HIT: Baseline Data
Habits/Meds
Cigarettes 21%
DM (Hx) 25%
ASA 82%
? blocker 43%
ACEI 21%
Demographics
BMI 29 + 5
WHR 0.96 + 0.05
Lipids
HDL-C 32 mg/dl
LDL-C 111 mg/dl
TG 161 mg/dl
Rubins HB et al. N Engl J Med 1999;341:410-418.
VA-HIT: Results
Rubins HB et al. N Engl J Med 1999;341:410-418.
Statin–Fibrate Therapy of Familial Combined Hyperlipidemia
Athyros VG et al. Am J Cardiol 1997;80:608-613.
Statin plus Fibrate Combination Therapy
May be associated with a greater risk of myopathy and rhabdomyolysis
The myopathy risk is enhanced under these situations: - High doses of statins - Renal insufficiency (Cr > 2.0) - Concomitant medications: Itraconazole, Ketoconazole Cyclosporin A Erythromycin
- Age > 70 years