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  1. Alistair Lindsay, Editor

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JUPITER puts primary prevention into new orbit

Current guidelines recommend statin treatment for patients with known vascular disease, diabetes or raised lipid levels. Yet half of myocardial infarctions and strokes occur in apparently healthy people with levels of low-density lipoprotein (LDL) cholesterol that are below current threshold levels for treatment. High-sensitivity C-reactive protein (CRP) is an inflammatory biomarker which can predict future vascular events and improves risk classification independently of LDL cholesterol level. In addition, statin therapy is known to lower CRP levels. However, a question remains to be answered: Would healthy people with levels of LDL cholesterol below current treatment levels but with raised levels of high-sensitivity CRP benefit from statin therapy?

The JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial—a randomised, double-blind, placebo-controlled, multicentre trial conducted at 1315 sites in 26 countries—sought to answer this question. A total of 17 802 apparently healthy people with LDL levels <3.4 mmol/l and high-sensitivity CRP levels ⩾2.0 mg/l were randomly assigned to either rosuvastatin 20 mg or placebo. The primary outcome was the occurrence of a first major cardiovascular event defined as non-fatal myocardial infarction, non-fatal stroke, hospitalisation for unstable angina, an arterial revascularisation procedure, or confirmed death from cardiovascular causes.

Follow-up was planned for 4 years but this was terminated early, at 1.9 years, when the data and safety monitoring board noticed a significant reduction in the primary end point among subjects assigned to receive rosuvastatin (142 primary events vs 251 in the placebo arm, hazard ratio (HR) = 0.56, 95% CI 0.46 to 0.69). A similar reduction was also seen in the so called “hard outcomes” of myocardial infarction, stroke or death from cardiovascular causes (83 events in the rosuvastatin group vs 157 in the placebo group, HR = 0.53, 95% CI 0.40 to 0.69). The rosuvastatin group did not have a higher incidence …

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