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Role of Rosuvastatin in the Treatment of Dyslipidemia

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... CHD Do Not Come Close to Achieving ATP II LDL-C Goal: L-TAP ... ATP III placed new emphasis on low HDL-C as a risk factor and potential target for intervention ... – PowerPoint PPT presentation

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Title: Role of Rosuvastatin in the Treatment of Dyslipidemia


1
Role of Rosuvastatin in the Treatment of
Dyslipidemia
  • Daniel J. Rader, MDAssociate Professor of
    Medicine
  • Director, Preventive Cardiology and Lipid
    ClinicUniversity of Pennsylvania School of
    Medicine

2
Evolution of Lipid Management GuidelinesThe
National Cholesterol Education Program (NCEP)
Adult Treatment Panel (ATP)
ATP I (1988)
ATP II (1993)
ATP III (2001)
Diet low-dose,nonstatin monotherapy
High-dose statin, combination therapy
Low- to moderate-dose statin monotherapy
Increasing aggressiveness of cholesterol-lowering
therapy
3
Most Patients Failed to Achieve ATP II LDL-C
Goals With Lipid-Lowering Therapy
lt 160 mg/dL
lt 130 mg/dL
100 mg/dL
Pearson TA, et al. Arch Intern Med.
2000160459-467Jacobson TA, et al. Arch Intern
Med. 20001601361-1369Sloan KL, et al. Am J
Cardiol. 2001881143-1146 Sueta CA, et al. Am
J Cardiol. 1999831303-1307.
4
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.
2000160459-467.
5
Many High Risk Patients Are Not Titrated or Do
Not Reach LDL-C Goal Even After Titration
2,989 high-risk patients(with known NCEPLDL-C
goal)
53 not at goalon starting dose (n 1575)
47 at goalon starting dose(n 1414)
53Not titrated(n 838)
47Titrated(n 737)
31Not at goal(n 478)
16at 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)
  • Only 47 of hypercholesterolemic patients
    treated with drug therapy are adequately
    controlled.

Ford et al. Circulation. 20031075185.
7
Many Patients With CHD Fail to Achieve LDL-C and
Non-HDL-C Goals Even With Dose TitrationACCESS
At Wk 54
n 2,543
Patients in CHD risk category. Ballantyne CM,
et al. Am J Cardiol. 200188265-269.
8
On-Treatment LDL-C Is Closely Related to CHD
Events in Statin Trials
pIac Placebo Rx Treatment. Adapted from
Ballantyne CM. Am J Cardiol. 1998823Q-12Q.
9
HPS Major Vascular Events in Highest and Lowest
LDL-C Tertiles and Effect of Therapy
8
Placebo
Simvastatin
Highest LDL-C tertile
Lowest LDL-C tertile
www.hpsinfo.org
10
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
Trials 24 - 26
Trials 27 - 28

P lt .05 vs comparators. Baseline TG 200
mg/dL.
12
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)
  • 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
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 lt 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
  • 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 ofHigh Blood Cholesterol in Adults.
JAMA. 20012852486-2497.
16
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
HDL-C Change From Baseline Rosuvastatin
Baseline HDL-C lt 40 mg/dL or 40 mg/dLTrial 65
STELLAR (Wk 6)
HDL-C lt 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
1 decreasein LDL-C reduces CHD risk by1
1 increasein HDL-C reduces CHD risk by3
Third Report of the NCEP Expert Panel. NIH
Publication No. 01-3670. 2001. http//hin.nhlbi.ni
h.gov/ncep_slds/menu.htm
19
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
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