Jupiter Trial

1. JUPITER
OVMC LANDMARK TRIALS SERIES
Ridker PM, et al. "Rosuvastatin to prevent vascular
events in men and women with elevated C-reactive
protein". The New England Journal of Medicine. 2008.
359(21):2195-2207.

2. The Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating
Rosuvastatin
(JUPITER)

3. BACKGROUND
 It is hypothesized that inflammatory pathways play a
role in atherosclerosis
 CRP is a marker of inflammation, and elevated levels
can predict future vascular events
 Sometimes cardiovascular events can still occur in
patients with normal LDL cholesterol
 Statins lower levels of CRP as well as cholesterol
 The JUPITER trial seeks to assess if statin (Rosuvastatin)
can benefit patients without hyperlipidemia but with
elevated CRP levels

4. CLINICAL QUESTION
In patients with normal LDL and elevated high-
sensitivity CRP (HS-CRP), does treatment with
Rosuvastatin (20mg qday) reduce the rate of first
major CV events?

5. DESIGN
 Analysis: Intention-to-treat
 Trial Design: Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial
 N=17,802 patients with normal LDL and elevated HS-CRP
 Rosuvastatin (n=8,901)
 Placebo (n=8,901)
 Powered to detect reduction in primary end point with 90% power
 Setting: 1315 centers in 26 countries
 Enrollment: 2003-2006
 Median follow-up: 1.9 years
 Primary outcome: Combined endpoint of first major CV event

6. POPULATION
Inclusion Criteria
 Men >50 years, or women >60 years
 LDL <130 mg/dL
 HS-CRP >2.0 mg/L
 Triglycerides <500 mg/dL
 No history of CV disease
Exclusion Criteria
 Usage of any lipid-lowering
 Hormone replacement therapy
 Diabetes
 SBP >190 mmHg or DBP >100 mmHg
 Cancer (except skin BCC) in the prior 5 years
 Alcohol or drug abuse
 Inflammatory conditions
 Use of immunosuppressants

7. INTERVENTIONS
 Randomization:
 Rosuvastatin 20mg qday
 Placebo
 Four-week placebo-only run-in phase: those who took more than 80% of their tablets were enrolled
in the trial
 Follow-up visits: to be scheduled at ~3 months then every 6 months after randomization until
month 60
 Telephone follow-ups and in-person visits
 Patients followed up in a close-out visit following cessation of the study

8. CRITICISMS/LIMITATIONS/FUNDING
 Many study participants were not on optimal medical therapy (eg, aspirin therapy if high
Framingham score)
 Excluded individuals with low/normal HS-CRP values (<2g/L)
 Did not include Asian participants, important because this group metabolizes rosuvastatin
differently
 Trial stopped early: only at 2 years, therefore may lead to effect overestimation
FUNDING:
AstraZeneca (makers of Crestor/Rosuvastatin)
Primary Author owns patent for HS-CRP assay

9. BOTTOM LINE
In patients without hyperlipidemia but
elevated high sensitivity CRP,
Rosuvastatin as PRIMARY
PREVENTIATION significantly reduces
the incidence of major CV events (eg
death, MI, stroke) at 2 years

10. DISCUSSION QUESTIONS
 What did the JUPITER trial suggest about
CRP levels and statin use?
 According to the JUPITER trial, should
patients without hyperlipidemia be
treated with statin?
 When studying rosuvastatin, why is it
recommended to have Asian
participants?
 Who funded the JUPITER Trial?

11. DISCUSSION QUESTIONS/ANSWERS
 What did the JUPITER trial suggest about hsCRP levels and statin use?
 ANSWER: There is a strong linear association with elevated hsCRP and ischemic stroke/vascular mortality. In
patients with elevated CRP levels at an increased risk of cardiovascular events, a statin is recommended
because statins lower hsCRP level.
 According to the JUPITER trial, should patients without hyperlipidemia be treated with statin?
 ANSWER: In a patient with normal LDL level but elevated high sensitivity CRP with increased risk of CV
events, a statin is recommended
 When studying rosuvastatin, why is it recommended to have Asian participants?
 ANSWER: Asian participants processs Rosuvastatin therapy differently. They are at increased risk of side
effects, especially myopathy may be increased. Therefore, half the standard dose may be recommended.

12. BOARD-LIKE QUESTION
61 yo man is evaluated for annual exam and asks
for advise on cardiac risk assessment. He denies
any current chest pain, SOB, PND, orthopnea. He
runs 4 miles ever 3 days and has never smoked.
He has no medical problems and does not take
any medications.
Cardiovascular risk calculation using Pooled
Cohort question is 7% risk of MI or CV event
within 10 years.
ADAPTED from MKSAP 17
QUESTION
What test should be performed on this patient?
A. Cardiac CT angiography
B. Cardiac Cath
C. Fractionated lipoprotein profile
D. High sensitivity CRP
E. Stress Echo

13. BOARD-LIKE QUESTION
Educational Objective:
High-sensitivity C-reactive (hsCRP) protein level
can guide treatment and cardiac risk stratification
in a patient at intermediate risk of cardiovascular
disease.
Key Point:
- Patients with hsCRP>1 are considered high
risk
- hsCRP<1 is considered low risk
- There is no role in evaluating lipid particle size
and number for targeting treatment regimen
ANSWER
What test should be performed on this patient?
A. Cardiac CT angiography
B. Cardiac Cath
C. Fractionated lipoprotein profile
D. High sensitivity CRP
E. Stress Echo

14. BOARD-LIKE QUESTION
Results of the tests showed elevated high
sensitivity CRP (7.4).
QUESTION
What is your next step?
A. Prescribe Aspirin
B. Prescribe Rosuvastatin
C. Prescribe Amlodipine
D. Perform a baseline EKG
E. Perform an ECHO

15. BOARD-LIKE QUESTION
Educational Objective:
In patients with elevated High-sensitivity C-
reactive (hsCRP) and normal lipids, Rosuvastatin
as primary prevention can reduce CV events at 2
years
QUESTION
What is your next step?
A. Prescribe Aspirin
B. Prescribe Rosuvastatin
C. Prescribe Amlodipine
D. Perform a baseline EKG
E. Perform an ECHO

16. REFERENCES
 Ridker PM, et al. "Rosuvastatin to prevent
vascular events in men and women with
elevated C-reactive protein". The New
England Journal of Medicine. 2008.
359(21):2195-2207.
 Brain, P. JUPITER. Retrieved March 5, 2017,
from
https://www.wikijournalclub.org/wiki/JUPITER
 MKSAP 17