Rosuvastatin

CARDIOVASCULAR BENEFITS WITH STATINS

VIEWING STATINS IN DIFFERENT PERSPECTIVES

Dr Jahanzaib Sheikh

Difference of Opinion leads to Inquire, and inquire leads to truth (Thomas Jefferson)

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Cardiology in Review • Volume 14, Number 2, March/April 2006

South Asians and CAD• South Asians have a higher prevalence

of CAD as compared with other ethnicities.

• South Asians may have a genetic predisposition to CAD

• Environmental, nutritional, and lifestyle factors may also be responsible.


Higher prevalence of: ◦ metabolic syndrome, ◦ Diabetes, insulin resistance◦ Central obesity◦ Dyslipidemias◦ Increased lipoprotein◦ Higher triglyceride levels◦ Increased thrombotic tendency (increased plasminogen

activator inhibitor-1◦ Decreased tissue plasminogen activator levels) and decreased

levels of physical activity.

South Asians


STUDY CONDUCTED AT:

Cardiology Department; The National Institute of Cardiovascular

Diseases (NICVD), Karachi.

Dr. Mazhar Mahmood, Dr. Tariq Ashraf, Dr Mohammad Anis Memon,

Dr. Abdul Samad Achakzai,

Abdominal obesity pattern among various ethnic groups presenting with acute coronary syndrome

EthnicityOthersMohajirBalochiPathanSindhiPunjabi

Pe

rce

nt

80.0%

60.0%

40.0%

20.0%

0.0%

36%

38%

41%32

%33%

22%

64%

62%59

%

68%

67%

78%

No Abdominal Obesity

Abdominal Obesity

Abdominal Obesity

Frequency of Abdominal Obesity in Ethnic Groups

Major, independent risk factors

Life-habit risk factors

Emerging risk factors

Categories of Risk Factors for CAD

National Cholesterol Education ProgramAdult Treatment Panel III (ATP III) Guidelines

Obesity (BMI 30)

Physical inactivity

Atherogenic diet

Life-Habit Risk Factors


Lipoprotein (a)

Homocysteine

Prothrombotic factors

Proinflammatory factors

Impaired fasting glucose

Subclinical atherosclerosis

Emerging Risk Factors


Cigarette smoking

Hypertension (BP 140/90 mmHg or on

antihypertensive medication)

Low HDL cholesterol (<40 mg/dL)†

Family history of premature CHD

◦ CHD in male first degree relative <55 years

◦ CHD in female first degree relative <65 years

Age (men 45 years; women 55 years)

Major Risk Factors (Exclusive of LDL Cholesterol) That Modify LDL Goals


In ATP III, diabetes is regarded as a

CHD risk equivalent. † HDL cholesterol 60 mg/dL counts as a “negative” risk factor; its

presence removes one risk factor from the total count.

Diabetes


Risk Category

CHD and CHD riskequivalents

Multiple (2+) risk factors

Zero to one risk factor

LDL Goal (mg/dL)

<100

<130

<160

Three Categories of Risk that Modify LDL-Cholesterol Goals


Most Patients Do Not Reach NCEP ATP III Target

Patients reaching

NCEP ATP IILDL

cholesterol target

(%)

Pearson TA et al. Arch Intern Med. 2000;160:459-467.

Low-risk(n=1143)

High-risk(n=2285)

CHD(n=1460)

All patients(N=4888)

68

37

18

38

0

20

40

60

80

100

ACCESS TRIAL: Many Patients With CHD Fail to Achieve LDL-C Goals Even With Dose Titration

0

10

20

30

40

50

60

70

80

90

100

LDL-C Non-HDL-C

Pat

ien

ts,

% a

t g

oal

Atorvastatin 10 - 80 mg

Simvastatin 10 - 40 mg

Lovastatin 20 - 80 mg

Fluvastatin 20 - 80 mg

Pravastatin 10 - 40 mg

†Patients in CHD risk category. Ballantyne CM, et al. Am J Cardiol. 2001;88:265-269.

n = 2,543†

At Wk 54

Proportions of patients achieving ATP III LDL-C goal <100 mg/dL at 16 weeks after switching to rosuvastatin (RSV) or remaining on atorvastatin (ATV) or simvastatin (SIM) after 8 weeks. *P < .001 for within-arm comparison of rosuvastatin vs atorvastatin or simvastatin.

C-Reactive Protein, a Sensitive Marker of Inflammation,

Predicts Future Risk of Coronary Heart Disease in Initially

Healthy Middle-Aged Men

Results From the MONICA (Monitoring Trends and Determinants in

Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992

Conclusions—These results confirm the prognostic relevance of CRP, a

sensitive systemic marker of inflammation, to the

risk of CHD in a large, randomly selected cohort of initially healthy middle-

aged men. They suggest that low-grade

inflammation is involved in pathogenesis of atherosclerosis, especially its

thrombo-occlusive complications.

(Circulation. 1999;99:237-242.)

Clinical Application of C-Reactive Protein for Cardiovascular Disease Detection

and PreventionPaul M Ridker

ISSN: 1524-4539Circulation 2003, 107:363-369

• Composed of five 23 kDa subunits, C-reactive protein (CRP) is an hepatically derived pentraxin that plays a key role in the innate immune response.

• CRP has a long plasma half-life and is now understood to be a mediator as well as a marker of atherothrombotic disease.

• Epidemiological studies carried out among individuals with no prior history of cardiovascular disease demonstrate that a single, non-fasting measure of CRP is a strong predictor of future vascular events

JUPITERBackground and Prior Work

Current guidelines for the prevention of myocardial infarction

stroke, and cardiovascular death endorse statin therapy

among patients with established vascular disease, diabetes,

and among those with hyperlidemia.

However, these screening and treatment strategies are

insufficient as half of all heart attack and stroke events occur

among apparently healthy men and women with average or

even low levels of cholesterol.

Ridker et al NEJM 2008

JUPITERAHA November 9, 2008

A Randomized Trial of Rosuvastatin in the Preventionof Cardiovascular Events Among 17,802 Apparently

Healthy Men and Women With Elevated Levels

of C-Reactive Protein (hsCRP):The JUPITER Trial

Paul Ridker*, Eleanor Danielson, Francisco Fonseca*, Jacques Genest*,

Antonio Gotto*, John Kastelein*, Wolfgang Koenig*, Peter Libby*,Alberto Lorenzatti*, Jean MacFadyen, Borge Nordestgaard*,

James Shepherd*, James Willerson, and Robert Glynn* on behalf of the JUPITER Trial Study Group

JUPITERPrimary Objectives

To investigate whether rosuvastatin 20 mg compared to

placebo would decrease the rate of first major cardiovascular

events among apparently healthy men and women with

LDL < 130 mg/dL (3.36 mmol/L) who are nonetheless

at increased vascular risk on the basis of an enhanced

inflammatory response, as determined by hsCRP > 2 mg/L.

Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin


Rosuvastatin 20 mg (N=8901) MIStroke

Unstable Angina

CVD DeathCABG/PTCA

JUPITERMulti-National Randomized Double Blind Placebo Controlled Trial of

Rosuvastatin in the Prevention of Cardiovascular EventsAmong Individuals With Low LDL and Elevated hsCRP

4-week run-in

Ridker et al, Circulation 2003;108:2292-2297.

No Prior CVD or DMMen >50, Women >60

LDL <130 mg/dL hsCRP >2 mg/L

JUPITERTrial Design

Placebo (N=8901)

Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Costa Rica,

Denmark, El Salvador, Estonia, Germany, Israel, Mexico, Netherlands,

Norway, Panama, Poland, Romania, Russia, South Africa, Switzerland,

United Kingdom, Uruguay, United States, Venezuela

JUPITERPrimary Trial Endpoint : MI, Stroke, UA/Revascularization, CV Death

Placebo 251 / 8901

Rosuvastatin 142 / 8901

HR 0.56, 95% CI 0.46-0.69P < 0.00001

- 44 %

0 1 2 3 4

0.0

00

.02

0.0

40

.06

0.0

8

Cu

mu

lati

ve I

ncid

en

ce

Number at Risk Follow-up (years)

RosuvastatinPlacebo

8,901 8,631 8,412 6,540 3,893 1,958 1,353 983 544 1578,901 8,621 8,353 6,508 3,872 1,963 1,333 955 534 174


JUPITERConclusions – Efficacy I

Among apparently healthy men and women with elevated hsCRP but

low LDL, rosuvastatin reduced by 47 percent incident

myocardial infarction, stroke, and cardiovascular death.

Despite evaluating a population with lipid levels widely considered

to be “optimal” in almost all current prevention algorithms, the

relative benefit observed in JUPITER was greater than in almost

all prior statin trials.

In this trial of low LDL/high hsCRP individuals who do not currently

qualify for statin therapy, rosuvastatin significantly reduced all-

cause mortality by 20 percent.


JUPITERConclusions - Safety

• With regard to safety , the JUPITER results

• show no increase in serious adverse events among those allocated to

rosuvastatin 20 mg as compared to placebo in a setting where half of the

treated patients achieved levels of LDL< 55 mg/dL (and 25 percent had LDL

< 44 mg/dL).

• show no increase in myopathy, cancer, hepatic disorders, renal disorders, or

hemorrhagic stroke with treatment duration of up to 5 years

• show no increase in systematically monitored glucose or glucosuria during

follow-up, but small increases in

• HbA1c and physician reported diabetes similar to that seen in other major

statin trials


JUPITERImplications for Primary Prevention

Among men and women age 50 or over :

If diabetic, treatIf LDLC > 160 mg/dL, treat

If hsCRP > 2 mg/L, treat

A simple evidence based approach to statin therapyfor primary prevention.


Patients who qualify for statin therapy are either not

being treated, being under-treated, or both.

Aggressive lipid lowering beyond current guidelines

appears to be more efficacious in reducing morbidity

& mortality.

Rosuvastatin is the most potent member of statin

family that has ability to regress Atherosclerosis.

Summary

Thank You

Thank You

Rosuvastatin

Health & Medicine

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