This document discusses cardiovascular disease (CAD) in South Asians and a clinical trial on the use of statins. It contains the following key points: 1) South Asians have a higher prevalence of CAD than other ethnicities due to genetic and environmental/lifestyle factors such as metabolic syndrome and central obesity. 2) The JUPITER trial found that treating individuals with low LDL cholesterol but high C-reactive protein with rosuvastatin reduced cardiovascular events like heart attack and stroke by 44% compared to placebo, showing statins can benefit those not currently eligible for treatment. 3) Rosuvastatin was well-tolerated in JUPITER and showed no increase in side effects even when LDL

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

3. • Recent Tv Talk Shows.
• Test Cricket Match
• Pharmaceutical Presnetation.
Cardiology in Review • Volume 14, Number 2, March/April 2006

5. • 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.
Cardiology in Review • Volume 14, Number 2, March/April 2006

6.  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.
Cardiology in Review • Volume 14, Number 2, March/April 2006

7.  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,

13.  Major, independent risk factors
 Life-habit risk factors
 Emerging risk factors
National Cholesterol Education Program
Adult Treatment Panel III (ATP III) Guidelines

14.  Obesity (BMI 30)
 Physical inactivity
 Atherogenic diet
National Cholesterol Education Program
Adult Treatment Panel III (ATP III) Guidelines

15.  Lipoprotein (a)
 Homocysteine
 Prothrombotic factors
 Proinflammatory factors
 Impaired fasting glucose
 Subclinical atherosclerosis
National Cholesterol Education Program
Adult Treatment Panel III (ATP III) Guidelines

16.  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)
National Cholesterol Education Program
Adult Treatment Panel III (ATP III) Guidelines

17. 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.
National Cholesterol Education Program
Adult Treatment Panel III (ATP III) Guidelines

18. Risk Category
CHD and CHD risk
equivalents
Multiple (2+) risk
factors
Zero to one risk
factor
LDL Goal
(mg/dL)
<100
<130
<160
National Cholesterol Education Program
Adult Treatment Panel III (ATP III) Guidelines

19. Most Patients Do Not Reach
NCEP ATP III Target
Patients
reaching
NCEP ATP II
LDL
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

20. 0
10
20
30
40
50
60
70
80
90
100
LDL-C Non-HDL-C
Patients,%atgoal
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

22. 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.

23. 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.)

24. Clinical Application of C-Reactive Protein for Cardiovascular Disease
Detection
and Prevention
Paul M Ridker
ISSN: 1524-4539
Circulation 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

25. JUPITER
Background 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

26. JUPITER
AHA November 9, 2008
A Randomized Trial of Rosuvastatin in the Prevention
of 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

27. JUPITER
Primary 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
Ridker et al NEJM 2008

28. Rosuvastatin 20 mg (N=8901) MI
Stroke
Unstable
Angina
CVD Death
CABG/PTCA
JUPITER
Multi-National Randomized Double Blind Placebo Controlled Trial of
Rosuvastatin in the Prevention of Cardiovascular Events
Among Individuals With Low LDL and Elevated hsCRP
4-week
run-in
Ridker et al, Circulation 2003;108:2292-2297.
No Prior CVD or DM
Men >50, Women >60
LDL <130 mg/dL
hsCRP >2 mg/L
JUPITER
Trial 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

29. JUPITER
Primary Trial Endpoint : MI, Stroke, UA/Revascularization, CV Death
Placebo 251 /
8901
Rosuvastatin 142 /
8901
HR 0.56, 95% CI 0.46-0.69
P < 0.00001
- 44 %
0 1 2 3 4
0.000.020.040.060.08
CumulativeIncidence
Number at Risk Follow-up (years)
Rosuvastatin
Placebo
8,901 8,631 8,412 6,540 3,893 1,958 1,353 983 544 157
8,901 8,621 8,353 6,508 3,872 1,963 1,333 955 534 174
Ridker et al NEJM 2008

30. JUPITER
Conclusions – 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.
Ridker et al NEJM 2008

31. JUPITER
Conclusions - 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
Ridker et al NEJM 2008

32. JUPITER
Implications for Primary Prevention
Among men and women age 50 or over :
If diabetic, treat
If LDLC > 160 mg/dL, treat
If hsCRP > 2 mg/L, treat
A simple evidence based approach to statin therapy
for primary prevention.
Ridker et al NEJM 2008

33.  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.

34. Thank
You