现代脂质三联治疗
Introduction
Part I
Efficacy - The Power to Reach Target
Key Factor,+ Differentiators,
LDL Reduction TG
HDL
LDL/HDL Ratio
The Lipid Triad
The LDL/HDL Ratio - Our Strength,Our Story!!
Clear positioning
for Lipobay
A new perception
of efficacy
Differentiation to
Atorvastatin
Fit with our
product profile
LDL HDL
Additional risk factor,
especially in diabetics
The Lipid Triad - Overview
TG
The Lipid Triad
The Ratio
The Lipid Triad
and Strategic Rationale
Part II
? No scientific evidence
? Evidence contradicting this statement
? A marketing hypothesis to build their LDL story
? Creating the perception of the statin with the
strongest efficacy
It’s logical
It’s measurable
It’s practicable
The Lipid Triad - The GP’s Perspective
Supporting Data
from Landmark Studies
Part III
12
10
8
6
4
2
0
%
Mo
rta
lity
Placebo Q1 Q2 Q3 Q4
(low HDL-increase) (high HDL-increase)
4S - Study
CAD Mortality per Quartiles of Increases in HDL-Cholesterol
KJEKSHUS J & PEDERSEN T (unpublished)
HDL Intervention Trial (VA-HIT)
RUBINS HB et al,New Engl J Med 1999; 341:410
0
6
-31
-4
-35
-30
-25
-20
-15
-10
-5
0
5
10
Cholesterol LDL-C HDL-C Triglycerides
Pe
rc
en
t c
ha
ng
e c
om
pa
re
d
to
pl
ac
eb
o
at
1 y
ea
r
Secondary Prevention in 2531 men
with low HDL-C & LDL-C showed a
22% reduction in combined fatal
and non-fatal MI
HDL - Cholesterol as Risk Factor for CHD
LRC - CPPT (Placebo) MRFIT (usual care)
Incidence rate of CHD Incidence rate of CHD 12
10
8
6
4
2
0
100 130 160 190
GORDON DJ et al,Circulation 1989; 79,8 - 15,
HDL - C
[mg / dl]
65
55
45
35
LDL - Cholesterol mg / dl LDL - Cholesterol mg / dl
12
10
8
6
4
2
0
100 130 160 190
0
0.5
1
1.5
2
2.5
3
Framingham Heart Study
CAD risk as a function of LDL-C and HDL-C
in men (50 to 70 y)
CASTELLI WP,Am J Cardiol 1998; 82:60-65
220 160 100
85
65
45
25
LDL Cholesterol (mg/dL)
0
2
4
6
8
10
12
14
16
LDL<=5 LDL>5 HDL>=1.08 HDL<1.08 LDL/HDL<=5 LDL/HDL>5
In
cid
en
ce
of
ca
rd
iac
ev
en
ts
(p
er
10
00
p
er
so
n-
ye
ar
s)
Gemfibrozil Placebo
LDL-C Tertiles (mmol/L) HDL-C Tertiles (mmol/L) LDL-C/HDL-C Tertiles
24 46 32 36 34 45 22 39 38 53 18 29
Incidence for cardiac events vs lipid parameter
Helsinki Heart Study
MANNINEN V,Leena T,Koskinen P et al,Circulation 1992; 85,37-45
AFCAPS/TEXCAPS
Apo B/A1
Tertiles
LDL-C/HDL-C
Tertiles
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
Ev
en
t R
ate
pe
r 1
00
Pa
tie
nt-
Ye
ars
of
Ri
sk
Ev
en
t R
ate
pe
r 1
00
Pa
tie
nt-
Ye
ars
of
Ri
sk
? 0.8889 0.8898-
1.0205
?1.0252 ? 3.7742 3.7744-
4.4096
??.4101
GOTTO A et al,Circulation 2000; 101,477-484
LDL/HDL Ratio as Therapeutic Success
Placebo
Statin
24
116
31
245
0
50
100
150
200
250
300
<= 5 > 5 LDL / HDL - Ratio
Triglycerides <200 mg/dl Triglycerides >= 200 mg/dl
CAD cases per 1,000 subjects in 6 years
ASSMANN G and SCHULTE H; Am J Cardiol 1992; 70,733-737
Incidence of CAD vs LDL/HDL ratio by TG level (n = 4559)
PROCAM Heart Study
0
50
100
150
200
250
300
<3 <4 <5 >5 >6 >7
LDL/HDL ratio
CH
D
In
cid
en
ce
/10
00
in
6
ye
ar
s
CHD risk according to LDL/HDL ratio at baseline
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag,1993,43
>5 High CHD risk Medium CHD risk Low CHD risk 3-5 <3
PROCAM Heart Study
Mean values for developing atherosclerotic CHD within 6 years
Variable CHD Development No CHD Development
(n = 186) (n = 4221)
TC (mg/dl) 251.8 222.9
HDL-C (mg/dl) 39.5 45.2
LDL-C (mg/dl) 176.2 147.1
LDL/HDL ratio 4.72 3.4
TG (mg/dl) 163.0 134.5
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag,1993,41
PROCAM Heart Study
Predictive value of risk factors for developing atherosclerotic
CHD within 6 years
Variable Risk Ratio Predictive Power %
TG ? 200 mg/dl 2.3 7.5
TC ? 250 (mg/dl) 2.8 8.3
LDL-C ? 195 (mg/dl) 3.7 12.0
LDL-C ? 155 (mg/dl) 3.3 7.1
HDL-C ? 35 (mg/dl) 3.9 11.0
LDL/HDL ratio ? 5 6.4 16.5
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag,1993,43
PROCAM Heart Study
HDL as CHD risk factor showed 186 events,
in men aged 40 - 60 years (n = 4407)
CH
D
In
cid
en
ce
pe
r 1
,0
00
in
6
ye
ar
s
0
20
40
60
80
100
120
140
160
? 35 35 - 55 ? 55
HDL-C (mg/dL)
110
30 21
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag,1993,59
PROCAM Heart Study
LDL as CHD risk factor showed 177 events
in men aged 40 - 60 years,( n = 4263)
CH
D
In
cid
en
ce
pe
r 1
,0
00
in
6
ye
ar
s
0
20
40
60
80
100
120
140
? 135 135 - 154 155 - 195 ? 195
LDL-C (mg/dL)
54
30 16
31
120
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag,1993,60
PROCAM Heart Study
Expert Opinions
Part IV
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
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
The Lipid Triad - Expert Comments
Helsinki Heart Study
“The LDL/HDL ratio was the best single predictor of cardiac
events”
Manninen V,Leena T,Koskinen P et al,Circulation 1992;85,1,37
,Patients in the placebo group with triglyceride levels of ? 200 mg/dl
and an LDL/HDL ratio of ? 5.0 had by far the highest incidence of
cardiac events”
Gerd Assmann,Lipid Metabolism Disorders and Coronary Heart Disease,
MMV Medizin Verlag,1993
The Lipid Triad - Expert Comments
PROCAM
“The greatest difference,in relative terms,between the groups
with and without major coronary events was seen in the
LDL/HDL-ratio”
Assmann G,Cullen P and Schulte H; Eur Heart Journal 1998,19 A2-A11
“For practical purposes it appears advisable to base predictions for
atherosclerotic CAD and treatment decision on a full lipid profile,
(cholesterol,triglycerides,LDL and HDL cholesterol) rather than
cholesterol or LDL cholesterol determinants alone”
Gerd Assmann,Lipid Metabolism Disorders and Coronary Heart Disease,
MMV Medizin Verlag,1993
The Lipid Triad - Expert Comments
State of the Art Conference,Berlin April 2000
“The Lipid Triad should form the bases of diagnostic and therapeutic decisions
in lipid therapy”
Markolf Hanefeld,Institute for Metabolism Disorders and Research,Dresden
“By just using high LDL as a criterion for prescription,some patients are
receiving statin treatment who do not need it,and those with low HDL and
high LDL who do need the treatment are not getting it!”
Gerd Assmann,Institute of Clinical Chemistry and Lab Medicine,Münster,Germany
The Lipid Triad - Expert Comments
The Impact
of Guidelines
Part V
The Lipid Triad - What the NCEP * Guidelines Say
HDL Cholesterol
? 35 mg/dl ( 0.9 mmol/l)
LDL Cholesterol
? 100 mg/dl ( 2.6 mmol/l)
TG
? 200 mg/dl (2.3 mmol/l)
* National Cholesterol Education Program targets for secondary prevention
The LDL/HDL Ratio - What the Guidelines say
Secondary Prevention Guidelines
NCEP (USA) LDL/HDL < 2.8
Association of Cardiology (Germany) LDL/HDL < 2.5
Society of Lipid Therapy (Germany) LDL/HDL < 3
Cerivastatin
Clinical Data
Part VI
Change in LDL/HDL Ratio
Datapool analysis,8 weeks
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
Baseline 0.1mg 0.2mg 0.3mg 0.4mg 0.8mg
n = 459
n = 636 n = 645
n = 1072 n = 732
LDL/HDL Ratio
Data on file
50
45
40
35
30
25
20
15
10
5
0
25.6
0.7
46.2
40.2
35.5
32.0
% Change in LDL/HDL Ratio
Datapool analysis,8 weeks
% Change in LDL/HDL Ratio
Placebo 0.1mg 0.2mg 0.3mg 0.4mg 0.8mg
Data on file
Baseline
LDL/HDL ratio After 8 weeks % of respondents
? 5 ? 5 12.3
? 3 69.9
? = 3 18.1
? 3 - ? = 5 ? 5 0.2
? 3 11.4
? = 3 88.5
? = 3 ? 3 0.5
? = 3 99.5
LDL/HDL Responder Rates
0.4 mg responder rate at 8 weeks (n = 941)
Data on file
Baseline after 8 weeks
>5 High CHD risk
Medium
CHD risk
Low
CHD risk
8%
60%
32%
90%
9%
1%
3-5
<3
LDL / HDL
Moving patients into the safety area after 8 weeks (n = 187)
Reaching Target with LDL/HDL Ratio Reduction
OSE et al,Curr Med Res & Opinion 2000; 16 (2):80-87
LD
L-
C
(m
ea
n
%
ch
an
ge
fro
m
ba
se
lin
e
afte
r 2
4 w
ee
ks
) 10
-40
-30
-20
-10
0
-50 -44.4%
Men
( n = 200)
Women
( n = 102)
-37.0%
LDL Cholesterol Reduction From Baseline
OSE et al,Curr Med Res & Opinion 1999; 15 (3),231-43
LDL Reduction with 0.4 mg of Cerivastatin
90
80
70
60
50
40
30
20
10
0
29.7
87.4
70.7
49.5
? 30 ? 35 ? 40 ? 45
Cu
m
ula
tiv
e %
o
f r
es
po
nd
en
ts
LDL Responder Rates with 0.4 mg
LDL % reduction rates in patients aged 60 to 65 years (n = 156)
Data on file
0,0
2,0
4,0
6,0
8,0
10,0
12,0
14,0
16,0
18,0
<50 <40 <30
HDL baseline
HDL Responder Rates
>50
% HDL increase
Data on file
0.4 mg responder rate at 8 weeks
6.5
10.3
17.9
8.2
90
80
70
60
50
40
30
20
10
0
? 10
23.3
9.3
81.4
65.1
55.8
? 20 ? 30 ? 40 ? 50
TG responder rates for 0.4 mg
TG % reduction rates from baseline ? 300 mg/dl at 8 weeks ( n = 43)
Cu
m
ula
tiv
e %
o
f r
es
po
nd
en
ts
Data on file
-20
-10
0
-30
-40
5
placebo
0.3mg 0.4mg
<150 mg/dl 150-250 mg/dl >250 mg/dl
0.1mg 0.2mg
10
- 35
-25
-15
5
TG Reduction
STEIN E et al,Atherosclerosis 1999; 144 (S 1),A 37
-20,0
-10,0
0,0
-30,0
-40,0
5
Placebo
- 35,0
-25,0
-15,0
5,0
Apo B/ Apo A1 Cerivastatin Pooled Data
Data on file
0.1mg 0.2mg 0.3mg 0.4mg 0.8mg
n = 588 n = 259 n = 265 n = 573 n = 658 n = 599
2,0
-18.5
-22.4
-26.8
-29.1
-36.0
Patient Group Cerivastatin Placebo
100mg 200mg 300mg 400mg 800mg
-18.5
-16.9
-21.0
-19.6
-17.2
-21.9
-20.5
-22.8
-22.4
-20.6
-24.9
-23.0
-21.2
-26.0
-24.9
-26.6
-26.8
-25.9
-28.3
-25.5
-26.0
-29.5
-28.7
-30.3
-29.1
-28.0
-30.6
-23.2
-29.1
-30.7
-27.5
-33.2
-36.0
-35.3
-37.1
-32.3
-35.9
-37.1
-36.0
-38.5
All
Male
Female
? 40 Years
> 40 - < 65 Years
? 65 Years
Elderly patients
- male
- female
2.0
2.2
1.7
-0.5
2.7
1.1
1.2
1.0
Cerivastatin Studies 8 Weeks Minimum Treatment
Data on file
Sales supporting
activities
Gaining consensus from OL
Leading instead of Following
Database LDL/HDL ratio
Opinion Leaders
Private Cardiologists
GPs
Spreading the Story - Effectively
Press Internet Publications
Introduction
Part I
Efficacy - The Power to Reach Target
Key Factor,+ Differentiators,
LDL Reduction TG
HDL
LDL/HDL Ratio
The Lipid Triad
The LDL/HDL Ratio - Our Strength,Our Story!!
Clear positioning
for Lipobay
A new perception
of efficacy
Differentiation to
Atorvastatin
Fit with our
product profile
LDL HDL
Additional risk factor,
especially in diabetics
The Lipid Triad - Overview
TG
The Lipid Triad
The Ratio
The Lipid Triad
and Strategic Rationale
Part II
? No scientific evidence
? Evidence contradicting this statement
? A marketing hypothesis to build their LDL story
? Creating the perception of the statin with the
strongest efficacy
It’s logical
It’s measurable
It’s practicable
The Lipid Triad - The GP’s Perspective
Supporting Data
from Landmark Studies
Part III
12
10
8
6
4
2
0
%
Mo
rta
lity
Placebo Q1 Q2 Q3 Q4
(low HDL-increase) (high HDL-increase)
4S - Study
CAD Mortality per Quartiles of Increases in HDL-Cholesterol
KJEKSHUS J & PEDERSEN T (unpublished)
HDL Intervention Trial (VA-HIT)
RUBINS HB et al,New Engl J Med 1999; 341:410
0
6
-31
-4
-35
-30
-25
-20
-15
-10
-5
0
5
10
Cholesterol LDL-C HDL-C Triglycerides
Pe
rc
en
t c
ha
ng
e c
om
pa
re
d
to
pl
ac
eb
o
at
1 y
ea
r
Secondary Prevention in 2531 men
with low HDL-C & LDL-C showed a
22% reduction in combined fatal
and non-fatal MI
HDL - Cholesterol as Risk Factor for CHD
LRC - CPPT (Placebo) MRFIT (usual care)
Incidence rate of CHD Incidence rate of CHD 12
10
8
6
4
2
0
100 130 160 190
GORDON DJ et al,Circulation 1989; 79,8 - 15,
HDL - C
[mg / dl]
65
55
45
35
LDL - Cholesterol mg / dl LDL - Cholesterol mg / dl
12
10
8
6
4
2
0
100 130 160 190
0
0.5
1
1.5
2
2.5
3
Framingham Heart Study
CAD risk as a function of LDL-C and HDL-C
in men (50 to 70 y)
CASTELLI WP,Am J Cardiol 1998; 82:60-65
220 160 100
85
65
45
25
LDL Cholesterol (mg/dL)
0
2
4
6
8
10
12
14
16
LDL<=5 LDL>5 HDL>=1.08 HDL<1.08 LDL/HDL<=5 LDL/HDL>5
In
cid
en
ce
of
ca
rd
iac
ev
en
ts
(p
er
10
00
p
er
so
n-
ye
ar
s)
Gemfibrozil Placebo
LDL-C Tertiles (mmol/L) HDL-C Tertiles (mmol/L) LDL-C/HDL-C Tertiles
24 46 32 36 34 45 22 39 38 53 18 29
Incidence for cardiac events vs lipid parameter
Helsinki Heart Study
MANNINEN V,Leena T,Koskinen P et al,Circulation 1992; 85,37-45
AFCAPS/TEXCAPS
Apo B/A1
Tertiles
LDL-C/HDL-C
Tertiles
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
Ev
en
t R
ate
pe
r 1
00
Pa
tie
nt-
Ye
ars
of
Ri
sk
Ev
en
t R
ate
pe
r 1
00
Pa
tie
nt-
Ye
ars
of
Ri
sk
? 0.8889 0.8898-
1.0205
?1.0252 ? 3.7742 3.7744-
4.4096
??.4101
GOTTO A et al,Circulation 2000; 101,477-484
LDL/HDL Ratio as Therapeutic Success
Placebo
Statin
24
116
31
245
0
50
100
150
200
250
300
<= 5 > 5 LDL / HDL - Ratio
Triglycerides <200 mg/dl Triglycerides >= 200 mg/dl
CAD cases per 1,000 subjects in 6 years
ASSMANN G and SCHULTE H; Am J Cardiol 1992; 70,733-737
Incidence of CAD vs LDL/HDL ratio by TG level (n = 4559)
PROCAM Heart Study
0
50
100
150
200
250
300
<3 <4 <5 >5 >6 >7
LDL/HDL ratio
CH
D
In
cid
en
ce
/10
00
in
6
ye
ar
s
CHD risk according to LDL/HDL ratio at baseline
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag,1993,43
>5 High CHD risk Medium CHD risk Low CHD risk 3-5 <3
PROCAM Heart Study
Mean values for developing atherosclerotic CHD within 6 years
Variable CHD Development No CHD Development
(n = 186) (n = 4221)
TC (mg/dl) 251.8 222.9
HDL-C (mg/dl) 39.5 45.2
LDL-C (mg/dl) 176.2 147.1
LDL/HDL ratio 4.72 3.4
TG (mg/dl) 163.0 134.5
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag,1993,41
PROCAM Heart Study
Predictive value of risk factors for developing atherosclerotic
CHD within 6 years
Variable Risk Ratio Predictive Power %
TG ? 200 mg/dl 2.3 7.5
TC ? 250 (mg/dl) 2.8 8.3
LDL-C ? 195 (mg/dl) 3.7 12.0
LDL-C ? 155 (mg/dl) 3.3 7.1
HDL-C ? 35 (mg/dl) 3.9 11.0
LDL/HDL ratio ? 5 6.4 16.5
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag,1993,43
PROCAM Heart Study
HDL as CHD risk factor showed 186 events,
in men aged 40 - 60 years (n = 4407)
CH
D
In
cid
en
ce
pe
r 1
,0
00
in
6
ye
ar
s
0
20
40
60
80
100
120
140
160
? 35 35 - 55 ? 55
HDL-C (mg/dL)
110
30 21
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag,1993,59
PROCAM Heart Study
LDL as CHD risk factor showed 177 events
in men aged 40 - 60 years,( n = 4263)
CH
D
In
cid
en
ce
pe
r 1
,0
00
in
6
ye
ar
s
0
20
40
60
80
100
120
140
? 135 135 - 154 155 - 195 ? 195
LDL-C (mg/dL)
54
30 16
31
120
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag,1993,60
PROCAM Heart Study
Expert Opinions
Part IV
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
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
The Lipid Triad - Expert Comments
Helsinki Heart Study
“The LDL/HDL ratio was the best single predictor of cardiac
events”
Manninen V,Leena T,Koskinen P et al,Circulation 1992;85,1,37
,Patients in the placebo group with triglyceride levels of ? 200 mg/dl
and an LDL/HDL ratio of ? 5.0 had by far the highest incidence of
cardiac events”
Gerd Assmann,Lipid Metabolism Disorders and Coronary Heart Disease,
MMV Medizin Verlag,1993
The Lipid Triad - Expert Comments
PROCAM
“The greatest difference,in relative terms,between the groups
with and without major coronary events was seen in the
LDL/HDL-ratio”
Assmann G,Cullen P and Schulte H; Eur Heart Journal 1998,19 A2-A11
“For practical purposes it appears advisable to base predictions for
atherosclerotic CAD and treatment decision on a full lipid profile,
(cholesterol,triglycerides,LDL and HDL cholesterol) rather than
cholesterol or LDL cholesterol determinants alone”
Gerd Assmann,Lipid Metabolism Disorders and Coronary Heart Disease,
MMV Medizin Verlag,1993
The Lipid Triad - Expert Comments
State of the Art Conference,Berlin April 2000
“The Lipid Triad should form the bases of diagnostic and therapeutic decisions
in lipid therapy”
Markolf Hanefeld,Institute for Metabolism Disorders and Research,Dresden
“By just using high LDL as a criterion for prescription,some patients are
receiving statin treatment who do not need it,and those with low HDL and
high LDL who do need the treatment are not getting it!”
Gerd Assmann,Institute of Clinical Chemistry and Lab Medicine,Münster,Germany
The Lipid Triad - Expert Comments
The Impact
of Guidelines
Part V
The Lipid Triad - What the NCEP * Guidelines Say
HDL Cholesterol
? 35 mg/dl ( 0.9 mmol/l)
LDL Cholesterol
? 100 mg/dl ( 2.6 mmol/l)
TG
? 200 mg/dl (2.3 mmol/l)
* National Cholesterol Education Program targets for secondary prevention
The LDL/HDL Ratio - What the Guidelines say
Secondary Prevention Guidelines
NCEP (USA) LDL/HDL < 2.8
Association of Cardiology (Germany) LDL/HDL < 2.5
Society of Lipid Therapy (Germany) LDL/HDL < 3
Cerivastatin
Clinical Data
Part VI
Change in LDL/HDL Ratio
Datapool analysis,8 weeks
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
Baseline 0.1mg 0.2mg 0.3mg 0.4mg 0.8mg
n = 459
n = 636 n = 645
n = 1072 n = 732
LDL/HDL Ratio
Data on file
50
45
40
35
30
25
20
15
10
5
0
25.6
0.7
46.2
40.2
35.5
32.0
% Change in LDL/HDL Ratio
Datapool analysis,8 weeks
% Change in LDL/HDL Ratio
Placebo 0.1mg 0.2mg 0.3mg 0.4mg 0.8mg
Data on file
Baseline
LDL/HDL ratio After 8 weeks % of respondents
? 5 ? 5 12.3
? 3 69.9
? = 3 18.1
? 3 - ? = 5 ? 5 0.2
? 3 11.4
? = 3 88.5
? = 3 ? 3 0.5
? = 3 99.5
LDL/HDL Responder Rates
0.4 mg responder rate at 8 weeks (n = 941)
Data on file
Baseline after 8 weeks
>5 High CHD risk
Medium
CHD risk
Low
CHD risk
8%
60%
32%
90%
9%
1%
3-5
<3
LDL / HDL
Moving patients into the safety area after 8 weeks (n = 187)
Reaching Target with LDL/HDL Ratio Reduction
OSE et al,Curr Med Res & Opinion 2000; 16 (2):80-87
LD
L-
C
(m
ea
n
%
ch
an
ge
fro
m
ba
se
lin
e
afte
r 2
4 w
ee
ks
) 10
-40
-30
-20
-10
0
-50 -44.4%
Men
( n = 200)
Women
( n = 102)
-37.0%
LDL Cholesterol Reduction From Baseline
OSE et al,Curr Med Res & Opinion 1999; 15 (3),231-43
LDL Reduction with 0.4 mg of Cerivastatin
90
80
70
60
50
40
30
20
10
0
29.7
87.4
70.7
49.5
? 30 ? 35 ? 40 ? 45
Cu
m
ula
tiv
e %
o
f r
es
po
nd
en
ts
LDL Responder Rates with 0.4 mg
LDL % reduction rates in patients aged 60 to 65 years (n = 156)
Data on file
0,0
2,0
4,0
6,0
8,0
10,0
12,0
14,0
16,0
18,0
<50 <40 <30
HDL baseline
HDL Responder Rates
>50
% HDL increase
Data on file
0.4 mg responder rate at 8 weeks
6.5
10.3
17.9
8.2
90
80
70
60
50
40
30
20
10
0
? 10
23.3
9.3
81.4
65.1
55.8
? 20 ? 30 ? 40 ? 50
TG responder rates for 0.4 mg
TG % reduction rates from baseline ? 300 mg/dl at 8 weeks ( n = 43)
Cu
m
ula
tiv
e %
o
f r
es
po
nd
en
ts
Data on file
-20
-10
0
-30
-40
5
placebo
0.3mg 0.4mg
<150 mg/dl 150-250 mg/dl >250 mg/dl
0.1mg 0.2mg
10
- 35
-25
-15
5
TG Reduction
STEIN E et al,Atherosclerosis 1999; 144 (S 1),A 37
-20,0
-10,0
0,0
-30,0
-40,0
5
Placebo
- 35,0
-25,0
-15,0
5,0
Apo B/ Apo A1 Cerivastatin Pooled Data
Data on file
0.1mg 0.2mg 0.3mg 0.4mg 0.8mg
n = 588 n = 259 n = 265 n = 573 n = 658 n = 599
2,0
-18.5
-22.4
-26.8
-29.1
-36.0
Patient Group Cerivastatin Placebo
100mg 200mg 300mg 400mg 800mg
-18.5
-16.9
-21.0
-19.6
-17.2
-21.9
-20.5
-22.8
-22.4
-20.6
-24.9
-23.0
-21.2
-26.0
-24.9
-26.6
-26.8
-25.9
-28.3
-25.5
-26.0
-29.5
-28.7
-30.3
-29.1
-28.0
-30.6
-23.2
-29.1
-30.7
-27.5
-33.2
-36.0
-35.3
-37.1
-32.3
-35.9
-37.1
-36.0
-38.5
All
Male
Female
? 40 Years
> 40 - < 65 Years
? 65 Years
Elderly patients
- male
- female
2.0
2.2
1.7
-0.5
2.7
1.1
1.2
1.0
Cerivastatin Studies 8 Weeks Minimum Treatment
Data on file
Sales supporting
activities
Gaining consensus from OL
Leading instead of Following
Database LDL/HDL ratio
Opinion Leaders
Private Cardiologists
GPs
Spreading the Story - Effectively
Press Internet Publications
