Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein (JUPITER)

The JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial randomized 17,802 apparently healthy adults with LDL-C below 130 mg/dL but elevated high-sensitivity CRP (hs-CRP ≥2.0 mg/L) to rosuvastatin 20 mg or placebo, testing whether statin therapy could prevent cardiovascular events in a population selected by elevated inflammation rather than elevated LDL-C.

Rosuvastatin reduced LDL-C by 50%, hs-CRP by 37%, and major cardiovascular events (MI, stroke, arterial revascularization, hospitalization for unstable angina, cardiovascular death) by 44%. The trial was stopped early at 1.9 years due to unequivocal benefit, with a hazard ratio of 0.56. All-cause mortality was also significantly reduced.

The JUPITER results demonstrated that inflammatory risk — captured by hs-CRP — identifies a large population of individuals who appear low-risk by LDL-C criteria but are in fact at elevated cardiovascular risk and derive substantial benefit from statin therapy. The findings validated hs-CRP as a treatment decision tool beyond its role as a risk marker.

However, the early stopping of the trial has been criticized as potentially overstating the magnitude of benefit, and the selection of the LDL-C below 130 threshold created a population with lower absolute risk than typical primary prevention trials. The CRP-guided selection approach has influenced guidelines but has not been uniformly adopted.

We rate the evidence strong. A landmark RCT establishing that rosuvastatin substantially reduces cardiovascular events in individuals with elevated hs-CRP regardless of LDL-C level — validating inflammation-guided statin prescribing in primary prevention.