This large prospective study is the first to show that statin therapy can prevent cardiovascular (CV) events among individuals who do not have elevated lipid levels. The JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; NCT00239681) trial demonstrated that rosuvastatin 20 mg significantly reduced the rate of primary CV events in an apparently healthy population that had normal low-density lipoprotein (LDL) levels but elevated high-sensitivity C-reactive protein (hsCRP) levels. A maximum follow-up of 5 years had been planned for the study, but the data and safety monitoring committee stopped the trial early (in March 2008) due to an overwhelming benefit of rosuvastatin.

The double-blind, multicenter trial included 17,802 individuals who had no history of CV disease or diabetes and a normal LDL level (<130 mg/dL) but a high hsCRP level (≥2 mg/L). The age criterion was ≥50 years for men and ≥60 years for women. Approximately 38% of the study population was female and approximately 25% was black or Hispanic.

Patients were randomly assigned to receive either rosuvastatin 20 mg daily (8901 patients) or placebo (8901 patients). The primary endpoint was the occurrence of a first major CV event, defined as nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for unstable angina, revascularization procedures, or confirmed death from CV causes.

Paul Ridker, MD, Brigham and Women's Hospital, Boston, MA, the lead author of the study, reported that at a median follow-up of 1.9 years, 142 events had occurred in the rosuvastatin group, compared with 251 in the placebo group, for a rate of 0.77 versus 1.36 per 100 person-years of follow-up (HR, 0.56; 95% CI, 0.46 to 0.69; p<0.00001). Dr. Ridker noted that the number that was needed to treat to prevent the occurrence of 1 primary endpoint was 25 over a 5-year treatment period. This number is lower than that associated with treating hyperlipidemia in primary prevention, he said.

Rosuvastatin also was associated with lower rates of the prespecified secondary endpoints, which included the individual components of the composite endpoint, as well as death from any cause (Table 1). Dr. Ridker said that all-cause mortality was driven largely by CV events.

The benefit of rosuvastatin was consistent across several prespecified subgroups that were classified by baseline characteristics, such as age, sex, race, body-mass index, and smoking history. Among individuals who had an elevated hsCRP level (> 2 mg/L) and no other major risk factor (other than older age), the benefit of rosuvastatin was similar to that for individuals at higher risk (HR, 0.63; 95% CI, 0.44 to 0.92; p=0.01).

Rosuvastatin significantly reduced levels of hsCRP and LDL throughout the duration of the trial. At 4 years, the median hsCRP levels were 1.8 mg/L and 3.3 mg/L in the rosuvastatin and placebo groups, respectively (p<0.001); the corresponding median LDL levels were 55 mg/dL and 109 mg/dL (p<0.001).

Treatment with rosuvastatin appeared to be safe, as evidenced by a similar rate of serious adverse events in the 2 groups (15.2% vs 15.5%; p=0.60), including similar rates of myopathy (10 vs 9 cases), ALT elevation >3x ULN (23 vs 17), and newly diagnosed cancer (298 vs 314; p=NS for all). Deaths from cancer were lower with rosuvastatin (0.4% vs 0.7%; p=0.02). There was a higher incidence of physician-reported diabetes in the rosuvastatin group (3.0% vs 2.4%; p=0.01), a finding that was similar to that seen in other major statin trials.

The study results raise an important question: Should the indications for statin therapy be expanded? Dr. Ridker noted that expert panels will need to evaluate the results to determine whether screening guidelines should be modified.

A report on the study and an accompanying editorial were published in the November 20, 2008 issue of The New England Journal of Medicine and are available online ( www.nejm.org ).