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The Dawning of the Age of JUPITER?

Once again, a statin was clearly effective for primary prevention of cardiovascular events, but using CRP levels to determine treatment thresholds remains debatable.

High-sensitivity C-reactive protein, a biomarker of inflammation, independently predicts cardiovascular events. To find out whether treatment with rosuvastatin might decrease the rate of first major cardiovascular events in apparently healthy individuals, investigators for the manufacturer-sponsored Justification for the Use of Statins in Prevention: an Interventional Trial Evaluating Rosuvastatin (JUPITER) studied subjects who had high-sensitivity CRP levels 2 mg/L but not high cholesterol levels (LDL levels <130 mg/dL). Of 89,890 men and women who were screened for enrollment, 17,802 were randomly assigned to receive rosuvastatin (20 mg daily) or placebo. The trial was stopped after a median follow-up of 1.9 years when the data and safety monitoring committee noted a significant reduction in the primary endpoint — first occurrence of a major cardiovascular event, defined as nonfatal MI, nonfatal stroke, hospitalization for unstable angina, arterial-revascularization procedure, or confirmed death from cardiovascular causes — in the rosuvastatin group.

The study incorporated a diverse population (38.2% were women; 25.2% were black or Latino); 16.6% of participants took aspirin. When the study was terminated, 75% of participants were taking their assigned medications. In the rosuvastatin group, the median LDL level at 12 months was 55 mg/dL, and the mean high-sensitivity CRP level was 2.2 mg/L; in the placebo group, the median LDL level was 110 mg/dL and the median high-sensitivity CRP level was 3.5 mg/L. Overall, the rate of the primary endpoint was 0.77 per 100 person-years of follow-up in the rosuvastatin group and 1.36 per 100 person-years in the placebo group (P<0.00001). The rosuvastatin group also showed significant relative reductions in the rates of the individual components of the primary endpoint. The rate of death from any cause was 1.00 per 100 person-years in the rosuvastatin group and 1.25 per 100 person-years in the placebo group. Hazard ratios favored rosuvastatin for both sexes and for every subgroup studied. No between-group difference was seen in the rate of serious adverse events. Using Kaplan-Meier estimates, 95 patients would need to be treated with rosuvastatin for 2 years to prevent one occurrence of the primary endpoint. Over an average of 5 years of treatment, the number needed to treat to prevent one occurrence of the primary endpoint would be 25.

Comment: In JUPITER, statin therapy clearly was associated with significant reductions in relative risk for cardiovascular events. However, as noted in an accompanying editorial, when we weigh the costs and benefits of drug therapy, absolute differences in risk are more important than are relative differences. The results of JUPITER are inconclusive in regard to the value of high-sensitivity CRP testing in clinical care. At this time, no change is warranted to current guidelines recommending selective measurement of high-sensitivity CRP in asymptomatic patients at an intermediate level of risk based on standard clinical markers.

— Joel M. Gore, MD

Published in Journal Watch Cardiology November 10, 2008

Citation(s):

Ridker PM et al. for the JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008 Nov 9; [e-pub ahead of print]. (http://dx.doi.org/10.1056/NEJMoa0807646)

Hlatky MA. Expanding the orbit of primary prevention — Moving beyond JUPITER. N Engl J Med 2008 Nov 9; [e-pub ahead of print]. (http://dx.doi.org/10.1056/NEJMe0808320)