What is the JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) study?

What is the JUPITER Study?

The JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) study was a landmark randomized, double-blind, placebo-controlled trial that demonstrated rosuvastatin 20 mg daily reduced major cardiovascular events by 44% in apparently healthy individuals with normal LDL cholesterol (<130 mg/dL) but elevated high-sensitivity C-reactive protein (≥2 mg/L). 1

Study Design and Population

Key Enrollment Criteria:

• 17,802 participants from 26 countries (6,801 women, 38.2%) 2, 3
• Men ≥50 years and women ≥60 years without clinically evident cardiovascular disease 1
• LDL cholesterol <130 mg/dL (median 108 mg/dL) 2, 3
• High-sensitivity CRP ≥2 mg/L (median 4.3 mg/L) 1
• Excluded patients with diabetes or dyslipidemia 2

Baseline Risk Profile:

• Estimated 10-year coronary heart disease risk of 11.6% by Framingham criteria 1
• 58% had hypertension 2, 1
• 16% were current smokers 2
• 23% had low HDL cholesterol 1
• 32.1% had metabolic syndrome 3

Primary Results

The trial was stopped early after a median follow-up of only 1.9 years due to overwhelming benefit in the rosuvastatin group. 2, 1

Primary Composite Endpoint Reduction:

• 44% relative risk reduction (p<0.001) 1, 4
• 1.2% absolute risk reduction 1
• 252 events in placebo vs. 142 events in rosuvastatin group 1

Individual Component Outcomes:

• Nonfatal myocardial infarction: significantly reduced 1
• Nonfatal stroke: significantly reduced 1
• Arterial revascularization procedures: significantly reduced 1
• All-cause mortality: 20% reduction (p=0.02) 4
• No significant difference in cardiovascular death or unstable angina hospitalizations 1

Sex-Specific Analysis

JUPITER was notable for including the largest number of women in any primary prevention statin trial and performing sex-specific analyses. 2

Results by Sex:

• Women: Hazard ratio 0.54 (95% CI: 0.37-0.80, p=0.002) 2
• Men: Hazard ratio 0.58 (95% CI: 0.45-0.73, p<0.001) 2
• Women showed significant reductions specifically in revascularization and unstable angina rates 2

Lipid and Inflammatory Marker Changes

At one year, rosuvastatin produced:

• 50% reduction in LDL cholesterol (mean on-treatment level 55 mg/dL) 1, 4, 5
• 37% reduction in high-sensitivity CRP 4
• Increased HDL cholesterol 1
• Reduced total cholesterol and triglycerides (all p<0.001 vs. placebo) 1

Clinical Implications and Guideline Impact

The JUPITER trial fundamentally changed primary prevention guidelines by demonstrating benefit in a population that would not have qualified for statin therapy under previous guidelines. 2, 6

USPSTF Interpretation:

• JUPITER participants predominantly had traditional risk factors (hypertension 57%, smoking 15%) that the USPSTF prioritized for statin suitability 2
• The USPSTF does not recommend using CRP alone as a screening tool, as CRP is not included in major risk prediction calculators 2
• In the HOPE-3 trial, there was no difference in statin effects among participants with or without elevated CRP 2

ACC/AHA Guidelines:

• JUPITER provided evidence that rosuvastatin reduces cardiovascular events in persons with elevated CRP 2
• The trial required 17 men and 31 women to be treated for 5 years to prevent one MI, stroke, revascularization, or death 2
• For persons at low Framingham risk (<10%), 37 persons needed treatment for 5 years to prevent the same endpoints 2

Important Caveats and Limitations

Critical limitations that affect interpretation:

• JUPITER was not a trial of CRP screening, as persons with unknown or low CRP were not studied 2
• The trial was stopped early, resulting in short follow-up (median 1.9 years) 2, 1
• Cost-effectiveness of CRP testing beyond the specific JUPITER population has not been established 2
• A post-hoc analysis of subjects with elevated CRP but no other traditional risk factors (except age) showed no significant treatment benefit after adjustment for high HDL cholesterol 1

Safety Considerations:

• JUPITER provided crucial long-term safety data for patients achieving very low LDL cholesterol levels (<50 mg/dL) 3
• The trial was the first large prospective statin study to show benefit in reducing venous thromboembolism 4
• Increased physician-reported diabetes represents a safety concern with potent statins 6

Subgroup Analyses

Post-hoc analyses identified populations with greater benefit:

• Subjects at "intermediate" or "high" 10-year Framingham risk 6
• Those achieving both LDL cholesterol <70 mg/dL and CRP <1 mg/L post-treatment 6
• Patients ≥70 years of age 6
• Those with moderate chronic kidney disease (eGFR <60 mL/min/1.73 m²) 6

Role in Metabolic Syndrome

In the context of metabolic syndrome, JUPITER demonstrated:

• Patients with or without metabolic syndrome had similar reductions in cardiovascular events with rosuvastatin 2
• The trial included 5,577 participants with metabolic syndrome (32.1% of total) 3