1. Triglycerides
Cholesterol
HDL-C
or N
NIDDM
N or
or N
IDDM

2. Serum cholesterol (mmol/L)
MRFIT
150
Diabetic
100
CVD deaths per 10,000 man years 50
Non-diabetic
<4.5
4.5-
4.9
5.0-
5.4
5.5-
5.9
6.0-
6.4
6.5-
6.9
>7.0
Serum cholesterol (mmol/L)
Stamler et al, Diabetes Care 1993;16:434-44

3. Mean serum cholesterol mmol l-1
Cholesterol Levels and CHD Mortality
600
Finland
Ireland
500
England
New Zealand
Australia
Hungary
400
Denmark
Canada
Sweden
W. Germany
CHD mortality 10-5
Israel
300
Poland
Belgium
Italy
200
Switzerland
Yugoslavia
France
100
Japan
5.2
5.8
6.5
7.1
Mean serum cholesterol mmol l-1
Adapted from: Leon Simon, Am J Card 1986;May 30:Vol 57

4. 4S All-cause CHD Coronary mortality events revascularisation n
Effect of Treatment
All-cause CHD Coronary
mortality events revascularisation n
Diabetes* % % % ns p= p=0.005
IFG** % % % p= p= p=0.001
Non-diabetic % % % non IFG p= p< p<0.001
* fasting glucose 126 mg/dL (7.0 mmol/L)
** fasting glucose mg/dL ( mmol/L)
Haffner et al, Arch Intern Med 1999;159:2661-7

5. 4S Non-diabetic, IFG* Diabetes** non IFG
Placebo Simva Placebo Simva Placebo Simva
New CHD % % % % % % events
% actively % % % treated patients avoiding new CHD events
* FBG mmol/L
** FBG 7.0 mmol/L
Haffner et al, Arch Intern Med 1999;159:2661-7

6. CARE CHD mortality n & morbidity p-value Diabetes 586 -25% <0.05
IFG** % ns
Non-diabetic % <0.001 Non-IFG
* Expanded end-point
** Impaired fasting glucose mg/dL
Goldberg et al, Circulation 1998;98:2513-9

7. VA High-density Lipoprotein Cholesterol Intervention Trial (VA-HIT)
2531 men aged <74 years with CHD (MI 61%, CABG or PTC 57%; or coronary stenosis >50%)
HDL cholesterol <1.0 mmol/L (mean 0.83)
Triglyceride <3.4 mmol/L (mean 1.8)
LDL cholesterol <3.6 mmol/L (mean 2.9) (mean serum cholesterol 4.5)
Randomised to placebo or gemfibrozil 600 mg bd*
Duration 5.1 years
* gemfibrozil SR 1200 mg od initially
Bloomfield et al, N Eng J Med 1999;341:410-8

8. VA-HIT Cholesterol = 4.5 mmol/L HDL-C +8% CHD morbidity + mortality
LDL-C TG 0%
-4%
-22%
-31%
Bloomfield et al, N Eng J Med 1999;341:410-8

9. VA-HIT CHD & n stroke incidence p-value Diabetes 627 -24% 0.05
Non-diabetic %
Bloomfield et al, N Engl J Med 1999;341:410-8

10. * where resources permit (minimum standard of care >30%)
Indications for Statin Treatment in Diabetes Mellitus (no distinction between men and women)
Cholesterol >5 mmol/L + established CHD or other clinically significant atherosclerosis
Cholesterol >5 mmol/L + proteinuria
Cholesterol >5 mmol/L + CHD risk >15%* over next 10 years (=cardiovascular risk >20%)
* where resources permit (minimum standard of care >30%)

11. Clinical Trials of Lipid-lowering Drugs in Progress in Diabetes (November 2000)
HPS (Heart protection study)
1o (n=3985) 2o (n=1978)
Simvastatin / Antioxidants
FIELD (Fenofibrate Intervention
and Event Lowering in Diabetes 1o
Fenofibrate
CARDS (Collaborative AtoRvaStatin) 1o
Atorvastatin
ASPEN (981-71)
1o + 2o
Atorvastatin
LDS (Lipids in Diabetes Study) 1o
Cerivastatin / Fenofibrate

12. CARDS Study Design: Collaborative AtoRvastatin Diabetes Study
Patient Population
Type 2 diabetics
No prior MI or CAD
Other risk factors +
Lipid profile:
LDL-C <159 mg/dL (4.14 mmol/L)
TG <600 mg/dL (6.78 mmol/L)
Collaboration in the UK with DUK and NHS
d/b PBO
2,838 Patients
atorvastatin 10 mg
Min 4 years
The CARDS Study (Collaborative Atorvastatin Diabetes Study) is a second study in the clinical program looking at 2050 type II diabetics in the United Kingdom in association with the British Diabetes Association and the National Health Service.
These primary prevention patients, with no prior history of Myocardial Infarction or Coronary Artery Disease, but with additional risk factors, will be randomised to either atorvastatin 10mg or placebo. They will be followed for 4 years of treatment and the primary endpoint will be the assessment of time to a major cardiovascular event.
Primary Endpoint
Time to major CV event
(CHD death, non-fatal MI,
recanalization, CABG, Stroke)
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13. CARDS active sites
This map illustrates the broad distribution of CARDS sites .
The study has expanded considerably over the past 2 years and grown to a total of 134 sites across the UK and Ireland.
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14. CARDS sites - distribution
chart illustrate varied mix of CARDS sites involved across the UK and Ireland today.
Although we have introduced many primary care sites in recent years, HOSPITALS still make up the majority of the sites.
Together with the commercial sites also involved (Synexus and Chiltern),
right mix of sites to ensure not only
timely recruitment,
also quality data
ongoing patient care.
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15. CARDS Study – Current status
2838 Randomised patients
2298 ongoing in treatment
436 withdrawn from treatment
106 Deaths
Current withdrawal rate = 15.3 %