1. Role of Rosuvastatin in the Treatment of Dyslipidemia
Core Unmet Need (CM)
4/20/ :56 PM
Role of Rosuvastatin in the Treatment of Dyslipidemia
Daniel J. Rader, MD Associate Professor of Medicine
Director, Preventive Cardiology and Lipid Clinic University of Pennsylvania School of Medicine

2. Core Unmet Need (CM)
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Evolution of Lipid Management Guidelines: The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP)
ATP I (1988)
ATP II (1993)
ATP III (2001)
Diet; low-dose, nonstatin monotherapy
Low- to moderate-dose statin monotherapy
High-dose statin, combination therapy
Increasing aggressiveness of cholesterol-lowering therapy

3. Core Unmet Need (CM)
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Most Patients Failed to Achieve ATP II LDL-C Goals With Lipid-Lowering Therapy
< 160 mg/dL
< 130 mg/dL
≤ 100 mg/dL
Pearson TA, et al. Arch Intern Med. 2000;160: ; Jacobson TA, et al. Arch Intern Med. 2000;160: ; Sloan KL, et al. Am J Cardiol. 2001;88: ; Sueta CA, et al. Am J Cardiol. 1999;83:

4. Core Unmet Need (CM)
4/20/ :56 PM
Many Patients With CHD Do Not Come Close to Achieving ATP II LDL-C Goal: L-TAP
n = 1,460
Pearson TA, et al. Arch Intern Med. 2000;160:

5. Core Unmet Need (CM)
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Many High Risk Patients Are Not Titrated or Do Not Reach LDL-C Goal Even After Titration
2,989 high-risk patients† (with known NCEP LDL-C goal)
53% not at goal on starting dose
(n = 1575)
47% at goal on starting dose (n = 1414)
53% Not titrated (n = 838)
47% Titrated (n = 737)
31% Not at goal (n = 478)
16% at goal (n = 259)
†CHD and/or diabetes mellitus with high-density lipoprotein cholesterol (HDL-C) ≤ 45 mg/dL.
Simpson RJ Jr. Circulation 2001.

6. Cholesterol Treatment in NHANES (1999-2000)
Core Unmet Need (CM)
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Cholesterol Treatment in NHANES ( )
Only 47% of hypercholesterolemic patients treated with drug therapy are adequately controlled.
Ford et al. Circulation. 2003;107:5185.

7. Core Unmet Need (CM)
4/20/ :56 PM
Many Patients With CHD Fail to Achieve LDL-C and Non-HDL-C Goals Even With Dose Titration ACCESS
At Wk 54
n = 2,543†
†Patients in CHD risk category.
Ballantyne CM, et al. Am J Cardiol. 2001;88:

8. On-Treatment LDL-C Is Closely Related to CHD Events in Statin Trials
Core Unmet Need (CM)
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On-Treatment LDL-C Is Closely Related to CHD Events in Statin Trials
HPS-Rx
HPS-plac
CARE-Rx
4S-plac
4S-Rx
LIPID-plac
CARE-plac
LIPID-Rx
WOSCOPS-plac
WOSCOPS-Rx
AFCAPS-plac
ASCOT-plac
AFCAPS-Rx
ASCOT-Rx
2° prevention
1° prevention 5 10 15 20 25 30 80
100
120
140
160
180
200
Mean on-treatment LDL-C level at follow-up (mg/dL)
% with CHD event
CHD + revasc + stroke
CHD
pIac = Placebo; Rx = Treatment.
Adapted from Ballantyne CM. Am J Cardiol. 1998;82:3Q-12Q.

9. Core Unmet Need (CM) 8
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HPS: Major Vascular Events in Highest and Lowest LDL-C Tertiles and Effect of Therapy
Placebo
Simvastatin
Highest LDL-C tertile
Lowest LDL-C tertile

10. Medical Need in the Treatment of Dyslipidemia
Core Unmet Need (CM)
4/20/ :56 PM
Medical Need in the Treatment of Dyslipidemia
A need exists for more efficacious therapy to achieve
Greater LDL-C and non-HDL-C lowering at start dose

11. % of Patients Achieving Both LDL-C and Non-HDL-C ATP III Goals
Core Unmet Need (CM)
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% of Patients Achieving Both LDL-C and Non-HDL-C ATP III Goals
Trials
Trials *
*P < .05 vs comparators. Baseline TG ≥ 200 mg/dL.

12. Medical Need in the Treatment of Dyslipidemia
Core Unmet Need (CM)
4/20/ :56 PM
Medical Need in the Treatment of Dyslipidemia
A need exists for more efficacious therapy to achieve
Greater LDL-C and non-HDL-C lowering at start dose
Greater LDL-C and non-HDL-C lowering at maximal dose

13. Familial Hypercholesterolemia (FH)
Core Unmet Need (CM)
4/20/ :56 PM
Familial Hypercholesterolemia (FH)
FH is common
There are 500,000 patients in the US (frequency, 1 person in 500)
FH causes early CHD
Average age of CHD onset is 45 to 50 yr in men, 55 to 60 yr in women
FH is difficult to treat
Most FH patients cannot be adequately treated to NCEP LDL-C goal

14. Stein et al. J Am Col Cardiol 2003.
Core Unmet Need (CM)
4/20/ :56 PM
% of High-Risk FH Patients Achieving NCEP ATP III LDL-C Goal in 2 Different Studies
Rosuvastatin 40 mg
Atorvastatin 40 mg + Ezetimibe 10 mg
Atorvastatin 80 mg
Atorvastatin 80 mg
Note: no statistical analyses were performed.
LDL-C: < 100 mg/dL (2.59 mmol/L).
Stein et al. J Am Col Cardiol 2003.

15. Low HDL-C Is Common and Represents an Important Medical Need
Core Unmet Need (CM)
4/20/ :56 PM
Low HDL-C Is Common and Represents an Important Medical Need
Low HDL-C is one of the most common risk factors in patients with premature CHD
ATP III placed new emphasis on low HDL-C as a risk factor and potential target for intervention
Modest increases in HDL-C may translate into substantial cardiovascular risk reduction
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:

16. Medical Need in the Treatment of Dyslipidemia
Core Unmet Need (CM)
4/20/ :56 PM
Medical Need in the Treatment of Dyslipidemia
A need exists for more efficacious therapy to achieve
Greater LDL-C and non-HDL-C lowering at start dose
Greater LDL-C and non-HDL-C lowering at maximal dose
Improved HDL-C raising

17. Core Unmet Need (CM)
4/20/ :56 PM
HDL-C: % Change From Baseline Rosuvastatin: Baseline HDL-C < 40 mg/dL or ≥ 40 mg/dL Trial 65 – STELLAR (Wk 6)
HDL-C < 40 mg/dL
HDL-C ≥ 40 mg/dL
Data presented as LS mean.

18. Relationship Between Changes in LDL-C and HDL-C Levels and CHD Risk
Core Unmet Need (CM)
4/20/ :56 PM
Relationship Between Changes in LDL-C and HDL-C Levels and CHD Risk
1% decrease in LDL-C reduces CHD risk by 1%
1% increase in HDL-C reduces CHD risk by 3%
Third Report of the NCEP Expert Panel. NIH Publication No

19. Role of Rosuvastatin in the Treatment of Dyslipidemia
Core Unmet Need (CM)
4/20/ :56 PM
Role of Rosuvastatin in the Treatment of Dyslipidemia
Greater LDL-C and non-HDL-C lowering at start dose
Greater LDL-C and non-HDL-C lowering at maximal dose
Improved HDL-C raising