Jupiter Trial

Dr Sheeraz Alam
DM Cardiology SR1
JNMCH, AMU
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.
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?
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
DESIGN

 Setting: 1315 centers in 26 countries

 Enrollment: Feb 2003- Dec 2006
 Median follow-up: 1.9 years (maximum 5.0)
Primary Endpoints

 First major Cardiovascular Events

Nonfatal MI
Nonfatal Stroke
Hospitalization for USA
Arterial revascularization procedure
Confirmed death from cardiovascular cause
Secondary Endpoints

 Includes the component of Primary Endpoints considered individually

Arterial revascularization
Hospitalization for USA
Myocardial infarction, stroke, or death from cardiovascular causes
Death from any cause
Inclusion Criteria

 Men >50 years, or women >60 years

 LDL <130mg/dL
 HS-CRP > 2.0mg/dL
 Triglycerides <500mg/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
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
Effect of Rosuvastatin on Lipids and HS-CRP
Outcomes
Primary Endpoints

 Shows cumulative incidence of

Primary Endpoints
 Hazard ratio for rosuvastatin, was
0.56 (95% confidence interval
[CI], 0.46 to 0.69; P<0.00001).
 Hazard ratio in the rosuvastatin
group was 0.53 (95% CI, 0.40 to
0.69; P<0.00001).
 Hazard ratio in the rosuvastatin
group was 0.53 (95% CI, 0.40 to
0.70; P<0.00001).
 Hazard ratio in the rosuvastatin
group was 0.80 (95% CI, 0.67 to
0.97; P=0.02).
Effect on Primary Endpoint, baseline chr
Adverse Events
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 population, because this group metabolizes rosuvastatin differently
 Trial stopped early: only at 2 yrs, therefore may lead to effect overestimation.

Funding- Astra Zeneca

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.
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