Among the pleiotropic effects of statins, plasma C-reactive protein (CRP) levels, which predict cardiovascular events, have been shown to be lowered by this class of drug. The JUPITER study examined whether rosuvastatin would prevent cardiovascular disease (myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death for cardiovascular causes) in a sample of 17,802 men and women with CRP levels ≥2.0 mg/l but LDL cholesterol levels <3.4 mmol/l. Subjects were randomized to rosuvastatin 20 mg daily or placebo and followed for 1.9 years. Rosuvastatin produced a 50% decrease in LDL cholesterol levels and a 37% decrease in CRP concentrations. Treatment with rosuvastatin was associated with a reduction in cardiovascular disease risk (hazard ratio: 0.56, 95% CI, 0.46-0.69, p<0.00001). While rosuvastatin-treated patients did not have a significant increase in myopathy or cancer, a higher incidence of physician-reported diabetes was reported in these patients. Although results of the JUPITER study were positive in terms of relative risk reduction, the magnitude of the benefit in terms of absolute risk reduction has been a topic of discussion since the publication of this landmark trial. This paper of the JUPITER trial was accompanied by an editorial by Mark A. Hlatky who raised the point that before pharmacological treatment is used for primary prevention, the evidence should be examined critically. Among others, the absolute benefits of treatment must be large enough to justify the associated risks and costs. Hlatky was concerned by the higher HbA1c levels and incidence of diabetes in patients who received rosuvastatin. Moreover, the long-term safety of rosuvastatin is unknown, particularly in low-risk subjects without clinical disease. Finally, the design of the JUPITER trial only provided limited and indirect information on the role of CRP testing in clinical management. JUPITER provided evidence about the effectiveness of statin therapy in reducing cardiovascular risk in individuals who otherwise would not have been considered for pharmacotherapy.
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