High tierRandomized Controlled TrialCitation verified
Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein
Paul M Ridker, Eleanor Danielson, Francisco A H Fonseca, Jacques Genest, Robert J Glynn, JUPITER Study Group - New England Journal of Medicine, 2008
A primary-prevention trial that selected people by inflammation (high hs-CRP) rather than high LDL. Rosuvastatin nearly halved the primary cardiovascular endpoint (HR 0.56). It is both a pillar of the "treat lower-risk people" case and a favourite skeptic target: it was industry-funded and stopped early, which tends to inflate the apparent effect.
Key findings
- Primary composite endpoint: HR 0.56 (95% CI 0.46-0.69, p<0.00001); 0.77 vs 1.36 events per 100 person-years.
- Death from any cause: HR 0.80 (95% CI 0.67-0.97).
- Higher incidence of physician-reported diabetes in the rosuvastatin group.
Effect measures
- Hazard Ratio: 0.56 (primary composite)95% CI 0.46-0.69
- Risk Difference: 0.77 vs 1.36 events per 100 person-years
- Hazard Ratio: 0.80 (all-cause mortality)95% CI 0.67-0.97
Why this evidence tier (High)
- Risk of bias:
- Large double-blind randomized placebo-controlled trial, but stopped early for benefit, which tends to overestimate effect size.
- Precision:
- Many events; precise estimate, though early termination truncates follow-up.
- Directness:
- Hard clinical endpoints, but in an hs-CRP-selected population that is not a general low-risk sample.
- Consistency:
- Direction concordant with other statin trials; the magnitude is at the high end.
- Funding / COI:
- Funded by AstraZeneca; lead investigator holds patents on inflammatory-biomarker testing - a notable conflict.
A strong but heavily caveated result: large effect, but early stopping, industry funding, and inflammation-based selection all argue for cautious weighting in low-risk primary prevention.
- Population:
- 17,802 apparently healthy people (men >=50, women >=60) with LDL <130 mg/dL but elevated hs-CRP (>=2.0 mg/L); primary prevention selected by inflammation, not by LDL. Stopped early at median 1.9 years.
- Conflicts of interest:
- Industry-funded by AstraZeneca. The lead investigator (Ridker) reported grants/consulting from AstraZeneca and others and is a co-inventor on patents for inflammatory-biomarker testing used to select participants.
- Funding:
- AstraZeneca (manufacturer of rosuvastatin).
Limitations
- Stopped early for benefit - apparent effect size is likely inflated.
- Participants selected by hs-CRP, not representative of unselected low-risk adults.
- Industry-funded with a notable investigator conflict; raised the diabetes signal.