调脂治疗

34 45 22 39
38 53 18 29
0
LDL<=5 LDL>5
HDL>=1.08 HDL<1.08 LDL/HDL<=5 LDL/HDL>5
MANNINEN V, Leena T, Koskinen P et al. Circulation 1992; 85: 37-45
AFCAPS/TEXCAPS
65 55 45 35
GORDON DJ et al. Circulation 1989; 79: 8 - 15.
Framingham Heart Study
CAD risk as a function of LDL-C and HDL-C in men (50 to 70 y)
3
2.5
2
1.5
1
Risk Ratio
2.3 2.8 3.7 3.3 3.9 6.4
Predictive Power %
7.5 8.3 12.0 7.1 11.0 16.5
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag, 1993: 43
300
Low CHD risk
<3
250
Medium CHD risk
3-5
High CHD risk
>5
CHD Incidence/1000 in 6 years
200
150
100
50
0
<3
<4
<5
>5
>6
>7
LDL/HDL ratio
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag, 1993: 43
PROCAM Heart Study
Incidence of CAD vs LDL/HDL ratio by TG level (n = 4559)
CAD cases per 1,000 subjects in 6 years
300 245
250
200
150
116
100
50
24
31
0
<= 5
LDL / HDL - Ratio
Fit with our product profile
Clear positioning for Lipobay
Differentiation to Atorvastatin
A new perception of efficacy
The Lipid Triad - Overview The Lipid Triad
40
30
21
20
0 35
35 - 55
55
HDL-C (mg/dL)
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag, 1993: 59
CHD Incidence per 1, 000 in 6 years
PROCAM Heart Study
strongest efficacy
The Lipid Triad - The GP’s Perspective
It’s logical
It’s measurable
It’s practicable
Part III
Supporting Data from Landmark Studies
4S - Study
The Lipid Triad - Expert Comments
ACCP, March 2000 “Low HDL is a better indicator of CHD than high LDL as seen in epidemiological studies such as the Framingham Study and recently the VA-HIT Study.” Sander Robins, University Medical Center, Boston “Landmark statin trials have shown consistent benefits on CHD reduction after raising HDL by 5 - 10% irrespective of LDL levels” Christie Ballantyne, Baylor College of Medicine, Houston
>5
Triglycerides <200 mg/dl Triglycerides >= 200 mg/dl
ASSMANN G and SCHULTE H; Am J Cardiol 1992; 70: 733-737
PROCAM Heart Study
CHD risk according to LDL/HDL ratio at baseline
-20
22% reduction in combined fatal
and non-fatal MI
-25
-30
-35
-31
RUBINS HB et al. New Engl J Med 1999; 341:410
HDL - Cholesterol as Risk Factor for CHD
LRC - CPPT (Placebo) Incidence rate of CHD
PROCAM Heart Study
Predictive value of risk factors for developing atherosclerotic CHD within 6 years
Variable
TG 200 mg/dl TC 250 (mg/dl) LDL-C 195 (mg/dl) LDL-C 155 (mg/dl) HDL-C 35 (mg/dl) LDL/HDL ratio 5
LDL as CHD risk factor showed 177 events
in men aged 40 - 60 years, ( n = 4263)
140
120
120
100
80
60
54
40
20
16
0 135
31 30
135 - 154
155 - 195
LDL-C (mg/dL)
195
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag, 1993: 60
Incidence for cardiac events vs lipid parameter
Gemfibrozil Placebo
LDL-C Tertiles (mmol/L) HDL-C Tertiles (mmol/L) LDL-C/HDL-C Tertiles
16
14
12
10
8
6
4
2 24 46 32 36
PROCAM Heart Study
Mean values for developing atherosclerotic CHD within 6 years
Variable
TC (mg/dl) HDL-C (mg/dl) LDL-C (mg/dl) LDL/HDL ratio TG (mg/dl)
Part IV
Expert Opinions
The Lipid Triad - Expert Comments
AHA, November 1999 “Evaluating the risk on the bases of LDL alone, is naive” Valentin Fuster, Mount Sinai Medical Center, New York “The LDL/HDL ratio is a much stronger predictor for the CHD risk than LDL alone” Paul Ridker, Brigham Institute for Women’s Hospital, Boston
0.5
0Biblioteka Baidu
220
160
100
LDL Cholesterol (mg/dL)
CASTELLI WP. Am J Cardiol 1998; 82:60-65
25 45 65 85
Incidence of cardiac events (per 1000 person-years)
Helsinki Heart Study
The Lipid Triad - Expert Comments
Helsinki Heart Study “The LDL/HDL ratio was the best single predictor of cardiac
CHD Development (n = 186)
251.8 39.5 176.2 4.72 163.0
No CHD Development (n = 4221)
222.9 45.2 147.1 3.4 134.5
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag, 1993: 41
(high HDL-increase)
HDL Intervention Trial (VA-HIT)
Percent change compared to placebo at 1 year
Cholesterol LDL-C 10
5
0
0
HDL-C Triglycerides
6
-5
-4
-10
-15
Secondary Prevention in 2531 men with low HDL-C & LDL-C showed a
现代脂质三联治疗
Part I
Introduction
Efficacy - The Power to Reach Target
Key Factor:
LDL Reduction
+
Differentiators:
TG
HDL
LDL/HDL Ratio
The Lipid Triad
The LDL/HDL Ratio - Our Strength, Our Story!!
LDL
HDL
TG
The Ratio
Additional risk factor, especially in diabetics
Part II
The Lipid Triad and Strategic Rationale
• No scientific evidence • Evidence contradicting this statement • A marketing hypothesis to build their LDL story • Creating the perception of the statin with the
CHD Incidence per 1, 000 in 6 years
PROCAM Heart Study
HDL as CHD risk factor showed 186 events,
160
in men aged 40 - 60 years (n = 4407)
140
120
110
100
80
60
LDL/HDL Ratio as Therapeutic Success
Event Rate per 100 Patient-Years of Risk Event Rate per 100 Patient-Years of Risk
Apo B/A1 Tertiles
1.6
1.4 1.2
1
LDL-C/HDL-C Tertiles
CAD Mortality per Quartiles of Increases in HDL-Cholesterol 12
10
8
% Mortality
6
4
2
0
Placebo
Q1
Q2
(low HDL-increase)
KJEKSHUS J & PEDERSEN T (unpublished)
Q3
Q4
1.6
1.4
Placebo
1.2
1
Statin
0.8 0.6 0.4 0.2
0 0.8889 0.8898- 1.0252 1.0205
GOTTO A et al. Circulation 2000; 101: 477-484
0.8 0.6 0.4 0.2
0 3.7742 3.7744- .4101 4.4096
12
10
8
6
4
2
0 100 130 160 190 LDL - Cholesterol mg / dl
MRFIT (usual care) Incidence rate of CHD 12
10
8
6
4
2
0 100 130 160 190 LDL - Cholesterol mg / dl
HDL - C [mg / dl]