Published at www.nejm.org November 9, 2008 (10.1056/NEJMoa0807646)
Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein
Paul M Ridker, M.D., Eleanor Danielson, M.I.A., Francisco A.H. Fonseca, M.D., Jacques Genest, M.D., Antonio M. Gotto, Jr., M.D., John J.P. Kastelein, M.D., Wolfgang Koenig, M.D., Peter Libby, M.D., Alberto J. Lorenzatti, M.D., Jean G. MacFadyen, B.A., Børge G. Nordestgaard, M.D., James Shepherd, M.D., James T. Willerson, M.D., Robert J. Glynn, Sc.D., for the JUPITER Study Group
Editor's note: We invite readers to submit comments on the JUPITERtrial in a new interactive feature, Clinical Directions –The JUPITER Trial: Will You Change Your Practice? Commentingcloses November 26, 2008.
ABSTRACT
Background Increased levels of the inflammatory biomarker high-sensitivityC-reactive protein predict cardiovascular events. Since statinslower levels of high-sensitivity C-reactive protein as wellas cholesterol, we hypothesized that people with elevated high-sensitivityC-reactive protein levels but without hyperlipidemia might benefitfrom statin treatment.
Methods We randomly assigned 17,802 apparently healthy men andwomen with low-density lipoprotein (LDL) cholesterol levelsof less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivityC-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin,20 mg daily, or placebo and followed them for the occurrenceof the combined primary end point of myocardial infarction,stroke, arterial revascularization, hospitalization for unstableangina, or death from cardiovascular causes.
Results The trial was stopped after a median follow-up of 1.9years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levelsby 50% and high-sensitivity C-reactive protein levels by 37%.The rates of the primary end point were 0.77 and 1.36 per 100person-years of follow-up in the rosuvastatin and placebo groups,respectively (hazard ratio for rosuvastatin, 0.56; 95% confidenceinterval [CI], 0.46 to 0.69; P<0.00001), with correspondingrates 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 and0.77 for revascularization or unstable angina (hazard ratio,0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 forthe combined end point of myocardial infarction, stroke, ordeath 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 fromany 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 inmyopathy or cancer but did have a higher incidence of physician-reporteddiabetes.
Conclusions In this trial of apparently healthy persons withouthyperlipidemia but with elevated high-sensitivity C-reactiveprotein levels, rosuvastatin significantly reduced the incidenceof major cardiovascular events. (ClinicalTrials.gov number,NCT00239681
[ClinicalTrials.gov]
.)
Source Information
From the Center for Cardiovascular Disease Prevention (P.M.R., E.D., J.G.M., R.J.G.) and Division of Cardiovascular Medicine (P.M.R., P.L.), Brigham and Women's Hospital, Harvard Medical School, Boston; Universidade Federal de São Paulo, São Paulo (F.A.H.F.); McGill University Health Center, Montreal (J.G.); Weill Cornell Medical College of Cornell University, New York (A.M.G.); Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.); University of Ulm Medical Center, Ulm, Germany (W.K.); Hospital Cordoba, Cordoba, Argentina (A.J.L.); Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark (B.G.N.); University of Glasgow, Glasgow, Scotland (J.S.); and St. Luke's Episcopal Hospital–Texas Heart Institute, Houston (J.T.W.). This article (10.1056/NEJMoa0807646) was published at www.nejm.org on November 9, 2008. It will appear in the November 20 issue of the Journal.
Address reprint requests to Dr. Ridker at the Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA 02215, or at pridker{at}partners.org.
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