JUPITER: Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin

1. JUPITER: Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin  Purpose To evaluate whether people with low to normal levels of low-density lipoprotein cholesterol (LDL-C) and elevated levels of high-sensitivity C-reactive protein (hsCRP) would benefit from statin (rosuvastatin) treatment in terms of reducing major cardiovascular events. Reference Ridker PM, Danielson E, Fonseca FAH 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;359:2195–2207.

2. JUPITER: Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin - TRIAL DESIGN - Design Multicenter, multinational, randomized, double-blind, placebo-controlled trial. Patients 17,802 individuals with LDL-C levels of <130 mg/dL (3.4 mmol/L) and hsCRP levels of =2.0 mg/L. Individuals with a history of cardiovascular disease were excluded, as were those who had previously used lipid-lowering drugs. Follow-up and primary endpoint Combined primary endpoint of non-fatal myocardial infarction, non-fatal stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. Treatment Rosuvastatin 20 mg daily or placebo.

3. JUPITER: Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin - TRIAL DESIGN continued -

4. JUPITER: Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin - RESULTS - Primary endpoint and follow-up Upon the recommendations of an independent data-monitoring committee and the JUPITER steering committee, the trial was stopped prematurely after a median follow-up of 1.9 years (maximum of 5 years). At this point, there had been a significant reduction in the combined primary endpoint of major cardiovascular events among patients who had received rosuvastatin in comparison with those who had received placebo. Other endpoints There were significant reductions in the following outcomes: Fatal or non-fatal myocardial infarction Fatal or non-fatal stroke Arterial revascularization or unstable angina Myocardial infarction, stroke or CV death All-cause mortality Other results Rosuvastatin showed consistent benefit in all subgroups, according to age, race or ethnic group, region of origin, risk factor status and Framingham risk score, and it showed the first demonstrated benefit in women without established CHD. Relative risk reductions in the rosuvastatin group were similar for women (46%) and men (42%). The number of serious adverse events was similar between the two groups. There was no difference between treatment groups for muscle weakness, cancer, hematological disorders, gastrointestinal, hepatic or renal systems. However, there was a small but significant increase in investigator-reported diabetes in patients treated with rosuvastatin.

5. JUPITER: Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin - RESULTS -

6. JUPITER: Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin - RESULTS continued -

7. JUPITER: Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin - RESULTS continued -

8. JUPITER: Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin - SUMMARY - In individuals with low to normal levels of LDL-C and elevated levels of hsCRP, treatment with rosuvastatin significantly reduced the primary endpoint of major cardiovascular events. There was a 44% reduction in the primary endpoint of major cardiovascular events (a composite of CV death, MI, stroke, unstable angina, arterial revascularisation) in patients who received rosuvastatin 20 mg compared with those who received placebo (p<0.00001). A 20% reduction in total mortality was observed in patients who received rosuvastatin 20 mg compared with placebo (p=0.02). The number needed to treat with rosuvastatin for two years to prevent one primary endpoint is 95. Although there was no difference between treatment groups for muscle weakness, cancer, hematological disorders, gastrointestinal, hepatic or renal systems, there was a higher incidence of physician-reported diabetes in rosuvastatin treated patients.