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
0.0
00
.02
0.0
40
.06
0.0
8
Cu
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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
0.04
0.05
Cu
mu
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nci
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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
Cu
mu
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In
cid
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ce
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
Cu
mu
lati
ve In
cid
ence
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
Cu
mu
lati
ve I
nci
den
ce
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
0.06
Cu
mu
lati
ve I
nci
den
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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
.06
0.0
80
.10
Cu
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In
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0 1 2 3 4
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.
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