Statins lower risk of first cardiovascular event in patients with high C-reactive protein and normal LDL cholesterol

Objective. To determine whether statin treatment can lower cardiovascular events in men and women with normal low-density lipoprotein (LDL) cholesterol and elevated C-reactive protein levels. Design. Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), a randomized, double-blind, placebo-controlled trial. Setting and participants.17,802 men (aged ≥ 50 years) and women (aged ≥ 60 years) from 1315 sites in 26 countries with LDL cholesterol < 130 mg/dL, high-sensitivity-reactive protein(hs-CRP) level ≥ 2.0 mg/L, and triglycerides < 500 mg/dL were randomizedto either rosuvastatin 20 mg daily or placebo. Patients were excluded if they werecurrently or had previously been on lipid-lowering therapy or were actively beingtreated with hormone replacement therapy; had evidence of hepatic dysfunction,a creatine kinase level ≥ 3 times the upper limit of normal, serum creatininelevel ≥ 2.0 mg/dL; a recent history of alcohol or drug abuse, cancer within 5years, diabetes, uncontrolled hypertension or hypothyroidism, or an inflammatorydisorder such as severe arthritis, inflammatory bowel disease, orlupus; or wereon immunosuppressant therapy. Patients were included in thefinal sample ifthey had 80% compliance during a 4-week pla-cebo run-in period.At enrollment,the median LDL level was 108 mg/dL in both arms, andhs-CRP levels were 4.2 and 4.3 mg/L in the rosuvastatin and placebo arms,respectively. Mainoutcome measure. Combined primary endpoint of anycardiovascular event, including myocardial infarction,stroke,arterialrevascularization, hospitalization for unstable angina, or death fromcardiovascular causes. Main results. The trial was stopped short oftheplanned 4 years of follow-upbecause the prespecified number of primaryendpoints in the trial was reached earlier than expected. After a medianfollow-up of 1.9 years, patients in the rosuvastatin group had a 44% lower rateof the combined endpoint than the placebo group (0.77 vs. 1.36 person-years offollow-up, respectively; hazard ratio [HR], 0.56 [95% confidence interval {CI},0.46-0.69]; P < 0.001). The trend for a reduced rate ofcardiovascularoutcomes was evident for each of the individual outcomes aswell, including death from cardiovascular causes (HR, 0.53 [95% CI,0.40-0.69]; P< 0.001) and death from any cause (HR, 0.80 [95% CI,0.67-0.97]; P=0.02).Rosuvastatin decreased LDL cholesterol by 50% and hs-CRP by 37%. After 12months of follow-up, the median LDL cholesterol and hs-CRP levels were 55 mg/dL and 2.2 mg/L in the rosuvastatin arm as compared with 110 mg/dLand 3.5 mg/L in the placebo arm. Triglycerides were also significantly lower inthe rosuvastatin group at 1 year (99 mg/dL vs. 119 mg/dL). No increase inmyopathy or cancer was noted in the rosuvastatin group, although there was ahigher incidence of physician-reported diabetes. Conclusion. In patients with highhs-CRP and normal LDL cholesterol, statin treatment lowers the risk of majorcardiovascular events.