Presenter Disclosure Information Paul M Ridker, MD, FACC Dr Ridker is listed as a co-inventor on...

Presenter Disclosure InformationPaul M Ridker, MD, FACC

Dr Ridker is listed as a co-inventor on patents held by the Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease that have been licensed to Seimens and AstraZeneca. Dr Ridker is the Principal Investigator of JUPITER, an investigator initiated trial funded by AstraZeneca.

Dr Ridker has served as a consultant to AstraZeneca, Novartis, Merck, Schering Plough, ISIS, Vascular Biogenics (modest).

Dr Ridker has received grant support from the NHLBI, the NCI, the Donald W Reynolds Foundation, the Doris Duke Foundation, the Leducq Foundation, AstraZeneca, SanofiAventis, Novartis and Merck (significant)

Controversies in Prevention: The JUPITER Trial Controversies in Prevention: The JUPITER Trial Will it Change Your Practice? Will it Change Your Practice?

Primary Results and ImplicationsPrimary Results and Implications

Paul M Ridker, MD, MPHPaul M Ridker, MD, MPHEugene Braunwald Professor of MedicineEugene Braunwald Professor of Medicine

Director, Center for Cardiovascular Disease PreventionDirector, Center for Cardiovascular Disease Prevention

Brigham and Women’s HospitalBrigham and Women’s Hospital

Harvard Medical School, Boston, MA USAHarvard Medical School, Boston, MA USA

Dr Ridker is listed as a co-inventor on patents held by the Brigham and Women’s Hospital

that relate to the use of inflammatory biomarkers in cardiovascular disease and diabetes.

Sachdeva et al, Am Heart J 2009;157:111-7.e2.

LDLC Levels in 136,905 Patients Hospitalized With CAD: 2000- 2006

LDLC (mg/dL) 130-160 > 160< 130

Rosuvastatin 20 mg (N=8901)Rosuvastatin 20 mg (N=8901) MIMIStrokeStroke

UnstableUnstable AnginaAngina

CVD DeathCVD DeathCABG/PTCACABG/PTCA

JUPITERJUPITERMulti-National Randomized Double Blind Placebo Controlled Trial of Multi-National Randomized Double Blind Placebo Controlled Trial of

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

4-week 4-week run-inrun-in

No Prior CVD or DMNo Prior CVD or DMMen Men >>50, Women 50, Women >>6060

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

JUPITERTrial Design

Placebo (N=8901)Placebo (N=8901)

Baseline LDLC 104 mg/dLBaseline HDLC 49 mg/dLBaseline hsCRP 4.2 mg/L

Women 6,800Non-Caucasian 5,000 Ridker et al, NEJM 2008359:2195-07

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

Number Needed to Treat (NNT5) = 25

- 44 %

0 1 2 3 4

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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

JUPITERMyocardial Infarction, Stroke, Cardiovascular Death

Placebo (N = 157)

Rosuvastatin (N = 83)

HR 0.53, 95%CI 0.40-0.69P < 0.00001

- 47 %

0 1 2 3 4

0.00

0.01

0.02

0.03

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Number at Risk Follow-up (years)

Rosuvastatin

Placebo

8,901 8,643 8,437 6,571 3,921 1,979 1,370 998 551 159

8,901 8,633 8,381 6,542 3,918 1,992 1,365 979 550 181

JUPITERFatal or Nonfatal Myocardial Infarction

Rosuvastatin

Placebo

- 55 %

0 1 2 3 4

Follow-up Years

0.0

00

0.0

05

0.0

10

0.0

15

0.0

20

0.0

25

0.0

30

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HR 0.45, 95%CI 0.30-0.70P < 0.0002

JUPITERFatal or Nonfatal Stroke

Rosuvastatin

Placebo

- 48 %

0 1 2 3 4

Follow-up Years

0.00

00.

005

0.01

00.

015

0.02

00.

025

0.03

0

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HR 0.52, 95%CI 0.34-0.79P = 0.002

JUPITERBypass Surgery / Angioplasty

Placebo (N = 131)

Rosuvastatin (N = 71)

HR 0.54, 95%CI 0.41-0.72P < 0.00001

- 46 %

0 1 2 3 4

0.00

0.01

0.02

0.03

0.04

0.05

0.06

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Number at Risk Follow-up (years)

Rosuvastatin

Placebo

8,901 8,640 8,426 6,550 3,905 1,966 1,359 989 547 158

8,901 8,641 8,390 6,542 3,895 1,977 1,346 963 538 176

JUPITERAll Cause Mortality

Placebo 247 / 8901

Rosuvastatin 198 / 8901

HR 0.80, 95%CI 0.67-0.97P= 0.02

- 20 %

0 1 2 3 4

0.00

0.01

0.02

0.03

0.04

0.05

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Number at Risk Follow-up (years)

RosuvastatinPlacebo

8,901 8,847 8,787 6,999 4,312 2,268 1,602 1,192 683 2278,901 8,852 8,775 6,987 4,319 2,295 1,614 1,196 684 246

JUPITERPrimary Endpoint – Understudied or “Low Risk” Subgroups

0.25 0.5 1.0 2.0 4.0

Rosuvastatin Superior Rosuvastatin Inferior

Women

Age > 70

Framingham Risk < 10 %

Black, Hispanic, Other

LDLC < 100 mg/dL

No Hypertension

All Participants

N HR (95%CI)

6,801 0.54 (0.37-0.80)

5,695 0.61 (0.46-0.82)

8,882 0.56 (0.38-0.83)

5,117 0.63 (0.41-0.98)

6,269 0.66 (0.47-0.92)

7,586 0.62 (0.44-0.87)

17,802 0.56 (0.46-0.69)

BMI < 25 mg/m2 4,073 0.59 (0.40-0.87)

No metabolic Syndrome 10,296 0.49 (0.37-0.65)

Elevated hsCRP Only 6,375 0.63 (0.44-0.92)

Understudied Subgroups

“Low Risk” Subgroups

JUPITERPrimary Endpoint According to Baseline Glucose Levels

HR 0.51, 95% CI 0.40-0.67P < 0.0001

Normal Fasting Glucose

HR 0.69, 95% CI 0.49-0.98P= 0.04

Impaired Fasting Glucose

0 1 2 3 4

Follow-up Years

0.0

00

.02

0.0

40

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0.0

80

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Follow-up Years

RosuvastatinRosuvastatin

PlaceboPlacebo

JUPITERNumber Needed to Treat (5 year)

Endpoint All

Primary Endpoint 25

Primary Endpoint, Mortality 22

MI, Stroke, CABG/PTCA, Death 23

MI, Stroke, Death 31

Benchmarks:Statins for hyperlipidemia 5-year NNT 40-60Diuretics 5-year NNT 80-100Beta-blockers 5-year NNT 120-160Aspirin Men 5-year NNT 220-270Aspirin Women 5-year NNT 280-330

JUPITERNumber Needed to Treat (5 year)

Endpoint All Men Women

Primary Endpoint 25 22 36

Primary Endpoint, Mortality 22 19 33

MI, Stroke, CABG/PTCA, Death 23 19 35

MI, Stroke, Death 31 25 59

Benchmarks:Statins for hyperlipidemia 5-year NNT 40-60Diuretics 5-year NNT 80-100Beta-blockers 5-year NNT 120-160Aspirin Men 5-year NNT 220-270Aspirin Women 5-year NNT 280-330

JUPITERNumber Needed to Treat (5 year)

Endpoint All FRS<10 FRS>10

Primary Endpoint 25 47 17

Primary Endpoint, Mortality 22 39 16

MI, Stroke, CABG/PTCA, Death 23 42 16

MI, Stroke, Death 31 67 22

Benchmarks:Statins for hyperlipidemia 5-year NNT 40-60Diuretics 5-year NNT 80-100Beta-blockers 5-year NNT 120-160Aspirin Men 5-year NNT 220-270Aspirin Women 5-year NNT 280-330

0

50

100

150

200

250

300

350

400

450

JUPITER

WOSCOPS

AFCAPS/TexCAPS

HTN - Diuretic

s

HTN – Beta Blockers

Aspirin - M

en

Aspirin - W

omen

Estimated 5-Year NNT Values for the Primary Prevention of Cardiovascular Disease In Middle-Aged Populations

JUPITERCan we improve and simplify guidelines for primary prevention?

www.reynoldsriskscore.org

JUPITERCan we simplify guidelines for statin therapy?

1. Strong recommendations for diet, exercise, and smoking cessation for any patient with or at risk for cardiovascular disease.

2. If there is prior MI, stroke, or known CVD, treat

3. If the patient is diabetic or has a very strong family history of premature atherothrombosis, treat

4. If LDLC > 160, TC:HDLC > 6, or hsCRP > 2, treat

5. Beyond these recommendations, referral to lipid specialist or cardiologist for further evaluation.

JUPITERACC 2009 - Late Breaking Clinical Trial Data

Do statins have antithrombotic or fibrinolytic effects?

Late Breaking Clinical Trials II Sunday 2:00 PM Hall A2

A Randomized Trial of Rosuvastatin in the Prevention of Venous Thormboembolism: The JUPITER Trial

Is the benefit observed in the JUPITERtrial associated with achieving a low level of LDLC,a low level of hsCRP, or

both? Late Breaking Clinical Trials V Monday 2:00 PM Hall

A2Dual Treatment Targets for LDLC and CRP After

InitiationOf Rosuvastatin: The JUPITER Trial

JUPITERPublic Health Implications

However, application of the simple screening and treatmentstrategy tested in the JUPITER trial over a five-year period could conservatively prevent more than 250,000 heart attacks, strokes, revascularization procedures, and cardiovascular deaths in the United States alone.

Simplified guidelines that advocate combined lifestyle andpharmacologic therapy in those groups where trial evidenceclearly supports a net benefit have the potential to greatlyimprove patient care and public health.

Exercise, diet, and smoking cessation remain the firstinterventions for those with elevated LDLC or hsCRP.

With thanks to the 17,802 patients and the >1,000 physicians worldwide for their effort and commitment to the JUPITER trial program.