Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.
Level 2 - randomized trial
Large multicenter randomized controlled trial.
PubMed 18997196 · doi:10.1056/NEJMoa0807646
What was done
A total of 17,802 apparently healthy men and women with LDL cholesterol below 130 mg/dL (3.4 mmol/L) and high-sensitivity C-reactive protein (hs-CRP) of 2.0 mg/L or higher were randomly assigned to receive rosuvastatin 20 mg daily or placebo. The primary outcome was a composite of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. The trial was terminated early after a median follow-up of 1.9 years (maximum 5.0 years).
What was found
Rosuvastatin reduced LDL cholesterol by 50% and hs-CRP by 37%. Primary end point rates were 0.77 per 100 person-years with rosuvastatin versus 1.36 with placebo (hazard ratio 0.56; 95% CI, 0.46 to 0.69; P<0.00001). Rosuvastatin also significantly reduced myocardial infarction (HR 0.46; 95% CI, 0.30 to 0.70; P=0.0002), stroke (HR 0.52; 95% CI, 0.34 to 0.79; P=0.002), arterial revascularization or unstable angina (HR 0.53; 95% CI, 0.40 to 0.70; P<0.00001), the combined endpoint of MI, stroke, or CV death (HR 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and all-cause mortality (HR 0.80; 95% CI, 0.67 to 0.97; P=0.02). There was no significant increase in myopathy or cancer, but rosuvastatin was associated with a higher incidence of physician-reported diabetes.
Why it matters
This trial established that statin therapy provides substantial primary prevention benefit in individuals with normal baseline LDL cholesterol levels if systemic inflammation, measured by hs-CRP, is elevated.
Limits
The trial was stopped early for efficacy, which can overestimate treatment effect sizes. Median follow-up was relatively short at 1.9 years, limiting assessment of long-term risks such as new-onset diabetes. Because only participants with elevated hs-CRP were enrolled, the study cannot distinguish whether the benefit was specific to elevated hs-CRP or simply reflects LDL lowering in low-risk individuals.
Cited by
- contradicts The JUPITER trial and related studies showed that patients with high LDL cholesterol but low C-reactive protein have a negligible risk of cardiovascular disease compared to those with both high LDL and high CRP.