- Journal club critique
- Open Access
To JUPITER and beyond: Statins, inflammation, and primary prevention
© BioMed Central Ltd 2010
- Published: 13 May 2010
Evidence-Based Medicine Journal Club
Edited by Eric B Milbrandt. University of Pittsburgh Department of Critical Care Medicine
Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto AM, Kastelein JJP, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ: Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. NEJM 2008, 359: 2195-2207 .
Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment.
To investigate whether treatment with rosuvastatin, 20 mg daily, as compared to placebo, would decrease the rate of first major cardiovascular events.
Randomized, double-blind, placebo-controlled, multicenter trial.
1315 sites in 26 countries.
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.
Subjects were randomly assigned to rosuvastatin, 20 mg daily, or placebo.
The primary outcome was the occurrence of a first major cardiovascular event, defined as myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. Secondary endpoints included the components of the primary end point considered individually as well as death from any cause.
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.
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.)
Statins reduced risk of first major cardiovascular event in healthy subjects with elevated hsCRP but without hyperlipidemia. Furthermore, their use appears to be cost-effective from a societal perspective. Even so, society may wish to focus on aggressive reduction of traditional risk factors (obesity, hypertension, diabetes) before broadly increasing statin use. Though the results of statin trials in infection and severe sepsis are anxiously anticipated, larger studies will be needed before statins are routinely recommend in the management of severe infections.
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