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JUPITER Crestor 20mg Versus Placebo in Prevention of Cardiovascular (CV) Events

Purpose The purpose of this study is to determine the safety and effectiveness of long-term therapy with rosuvastatin compared with a placebo, and to evaluate whether treatment with rosuvastatin might be effective in reducing the risk of major cardiovascular events.

Condition Elevated hs C-Reactive Protein

Intervention Drug: Rosuvastatin

Phase III

Study Type: Interventional Study Design: Prevention, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary Outcome Measures: Investigate whether long-term treatment with rosuvastatin compared with placebo will decrease the rate of major cardiovascular events

Secondary Outcome Measures: Investigate the safety of long-term treatment with rosuvastatin compared with placebo through comparisons of total mortality, noncardiovascular mortality, & adverse events

Investigate whether therapy with rosuvastatin reduces the incidence of diabetes mellitus, venous thromboembolic events, & the incidence of bone fractures.

Estimated Enrollment: 15000 Study Start Date: February 2003 Study Completion Date: August 2008 Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)

Detailed Description: AstraZeneca announced it has decided to stop the CRESTOR JUPITER clinical study early based on a recommendation from an Independent Data Monitoring Board and the JUPITER Steering Committee, which met on March 29, 2008. The study will be stopped early because there is unequivocal evidence of a reduction in cardiovascular morbidity and mortality amongst patients who received CRESTOR when compared to placebo.

Eligibility

Ages Eligible for Study:   50 Years and older Genders Eligible for Study:   Both Accepts Healthy Volunteers:   No

Criteria Inclusion Criteria:

Men 50 years or older, women 60 years or older Low to normal levels of low density lipoprotein (LDL) cholesterol (< 130mg/dL) Elevated levels of C-Reactive Protein (CRP) > 2.0 mg/L Exclusion Criteria:

History of cardiovascular or cerebrovascular events Active liver disease Diabetes mellitus Uncontrolled hypertension or hypothyroidism History of certain malignancies Chronic inflammatory conditions History of alcohol or drug abuse

Methods We randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily, or placebo and followed them for the occurrence of the combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes.

Results The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P<0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P=0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P=0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P=0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes.

Conclusions In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events. (ClinicalTrials.gov number, NCT00239681 [ClinicalTrials.gov] .)