HDL的临床试验
HDL and Coronary Heart Disease
Angiographic and Clinical Event Trials
Angiographic Trials of Combination Therapy
Cholesterol Lowering Atherosclerosis Study (CLAS)1
Diet and niacin + colestipol (vs diet and placebo)
188 men (aged 40–59 y), post-CABG
Nonsmokers or former smokers, nondiabetic, nonhypertensive
Total-C at entry: 185–350 mg/dL; drug responsive
Familial Atherosclerosis Treatment Study (FATS)2
Lovastatin + colestipol, niacin + colestipol, or conventional therapy
146 men (aged ? 62 y) with CAD and family history of CAD
ApoB ? 125 mg/dL
Average stenosis: 34%
1. Blackenhorn DH et al. JAMA. 1987;257:3233–3240
2. Brown G et al. N Engl J Med. 1990;323:1289–1298
Angiographic Trials of Combination Therapy Effects on Lipids
% change
Trial LDL-C HDL-C TG
CLAS
Placebo (2 y)1 ? 5* ? 2 ? 5*
Niacin + colestipol (2 y)1 ? 43* ? 37* ? 22*
Niacin + colestipol (4 y)2 ? 40?? ? 37?? ? 18§
FATS (2.5 y)3
Conventional ? 7** ? 6** ? 15
Niacin + colestipol ? 32* ? 41* ? 29*
Lovastatin + colestipol ? 45* ? 16? ? 9
Versus baseline: *P < 0.001; ?P < 0.01; ** P < 0.05; Versus placebo: ??P < 0.001; §P < 0.03
1. Blankenhorn DH et al. JAMA 1987;257:3233–3240
2. Cashin-Hemphill L et al. JAMA 1990;264:3013–3017
3. Brown BG et al. N Engl J Med 1990;323:1289–1298
Cholesterol-Lowering Atherosclerosis Study (CLAS) Univariate Apo Predictors of Coronary Progression
Mean (mg/dL)
Predictor Progressor Nonprogressor P value
Placebo
(n = 82: 49 progressors, 33 nonprogressors)
ApoB 128 116 0.03
ApoC-III (total) 12.4 10.3 0.03
ApoC-III (HS)* 5.9 4.9 0.03
Drug
(n = 80: 31 progressors, 49 nonprogressors)
ApoC-III (HS)* 6.4 7.5 0.05
*HS = heparin supernate (apoC-III in HDL)
Blankenhorn DH et al. Circulation 1990;81:470–476
Familial Atherosclerosis Treatment Study (FATS) Univariate Predictors of Change in Proximal Stenosis
Predictor r P value
ApoB 0.38 < 0.0001
LDL-C 0.27 <0.01
HDL-C -0.33 <0.001
ApoA-I -0.28 Not reported
Brown G et al. N Engl J Med 1990;323:1289–1298
Angiographic Trials of Fibrate Therapy
Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT)1
Bezafibrate vs placebo
92 male survivors of MI, aged < 45 y at time of event
Coronary angiography at baseline and after 2 and 5 y
Lopid Coronary Angiography Trial (LOCAT)2
Gemfibrozil vs placebo
395 men, post-CABG
Coronary angiography at baseline and after 32 mos
1. Ericsson CG et al. Lancet 1996;347:849–853
2. Frick MH et al. Circulation 1997;96:2137–2143
Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) Effect on Lipid Levels at 5 Years
Change from baseline: *P < 0.001; ?P = 0.551; **P = 0.020
Bez = bezafibrate 200 mg TID (n = 42); Plac = placebo (n = 39)
Ericsson CG et al. Lancet 1996;347:849–853
-14.0*
-3.5?
8.6**
-26.3*
-5.6
-2.2
-0.8
2.7
-30
-25
-20
-15
-10
-5
0
5
10
Total-C
LDL-C
HDL-C
Total-TG
Bez Plac
(266) (267)
Median
baseline (mg/dL):
Bez Plac
(180) (179)
Bez Plac
(34) (39)
Bez Plac
(216) (175)
Median % change from baseline
15
-35
Lopid Coronary Angiography Trial (LOCAT) Effect on Lipid Levels at 1 Year
*P < 0.001 for between-group difference and for change from baseline
Frick MH et al. Circulation 1997;96:2137–2143
-5.5*
-4.5*
21*
-36*
5.1
5.3
7.0
4.6
-40
-30
-20
-10
0
10
20
30
Total-C
LDL-C
HDL-C
TG
Gemfibrozil
Placebo
Mean % change from baseline
Angiographic Trial of Statin Therapy
Lipoprotein and Coronary Atherosclerosis Study (LCAS)
Fluvastatin versus placebo in patients with low versus higher HDL-C
Angiographic data from 339 patients:
68 with baseline HDL-C < 35 mg/dL
271 with baseline HDL-C ? 35 mg/dL
Ballantyne CM et al. Circulation 1999;99:736–743
Lipoprotein and Coronary Atherosclerosis Study (LCAS) Benefit of Statin Therapy in Patients With Low HDL-C
0.30
0.25
0.20
0.15
0.10
0.05
0
HDL-C ? 35 mg/dL
HDL-C ? 35 mg/dL
Fluvastatin
Placebo
Decrease in minimum lumen diameter (mm)
P = 0.09
P = 0.0004
P for interaction = 0.01
Ballantyne CM et al. Circulation 1999;99:736–743
-0.065
-0.274
-0.036
-0.083
Lipoprotein and Coronary Atherosclerosis Study (LCAS) Event-Free Survival
2.5
1.00
0.75
0.50
0.25
0.00
0
1
2
Probability of event-free survival
1.00
0.75
0.50
0.25
0.00
0
1
2
2.5
Probability of event-free survival
Fluvastatin
Fluvastatin
Placebo
Placebo
HDL-C ? 35 mg/dL
HDL-C ? 35 mg/dL
P = 0.002
P = 0.232
Time (y)
Time (y)
Ballantyne CM et al. Circulation 1999;99:736–743
Angiographic Trials in Patients With Low HDL-C Effects on Lipids
Trial (pts with Agent Baseline (mg/dL) % change
evaluable angiography) (dosage) LDL-C HDL-C LDL-C HDL-C
BECAIT (N = 81) Bezafibrate 180 34 ? 3.5 ? 9 (600 mg/d)
LOCAT (N = 372) Gemfibrozil 138 31 ? 4.5 ? 21 (1,200 mg/d)
LCAS (N = 339) Fluvastatin 146 43 ? 25 ? 9 (40 mg/d)
LCAS (HDL-C Fluvastatin 143 32 ? 25 ? 16 < 35 mg/dL) (40 mg/d)
(N = 68)
Ballantyne CM et al. Circulation 1999;99:736–743
Helsinki Heart Study
Primary-prevention, placebo-controlled trial to determine whether increasing HDL-C levels and decreasing LDL-C levels would reduce incidence of CHD
4,081 dyslipidemic men, aged 40–55 y
Subjects randomized to gemfibrozil (600 mg BID) or placebo
Study duration: 5 y
Frick MH et al. N Engl J Med. 1987;317:1237–1245
Helsinki Heart Study Incidence of CHD Events
Numbers inside bars indicate number of cardiac events in each subgroup
Manninen V et al. Circulation. 1992;85:37–45
Incidence of cardiac events
(per 1,000 person-years)
0
5
10
15
20
HDL-C ? 42
HDL-C ? 42
Gemfibrozil
Placebo
TG ? 200 TG ? 200
TG ? 200 TG ? 200
27
36
7
9
14
16
8
23
mg/dL:
Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)
Randomized, double-blind trial to compare lovastatin with placebo for prevention of first acute major coronary event in men and women without clinically evident atherosclerotic CVD
5,608 men and 997 women with average Total-C and LDL-C and below-average HDL-C
Downs JR et al. JAMA 1998;279:1615–1622
Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) C