MedWire News: The lipid-lowering drug rosuvastatin nearly halves the risk for major cardiovascular (CV) events in apparently healthy people who have normal lipid levels but raised levels of high-sensitivity C-reactive protein (hsCRP), the JUPITER study has found.
The study is being hailed as a landmark in view of its implications for primary prevention, because rosuvastatin dramatically reduced CV morbidity and mortality in patients who were considered to be at low CV risk and who would not qualify for lipid-lowering therapy under current guidelines.
JUPITER (Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin) was presented by Paul Ridker (Brigham and Women’s Hospital, Boston, MA) at the American Heart Association 2008 Scientific Sessions in New Orleans, LA, and was published simultaneously in the New England Journal of Medicine.
The study rationale was that hsCRP predicts CV events but that it is unknown whether reducing systemic inflammation, through statin therapy, benefits outwardly healthy, normolipidemic patients.
JUPITER was conducted at 1315 sites in 26 countries and enrolled 17,802 men (≥50 years) and women (≥60 years) without CV disease or diabetes, but with LDL cholesterol <130 mg/dl and hsCRP ≥2.0 mg.
Subjects were randomized to rosuvastatin 20 mg or placebo and monitored for the primary endpoint of major CV events (a composite of nonfatal MI, nonfatal stroke, unstable angina, revascularization, or CV death). Secondary endpoints were the individual components of the primary endpoint plus death from any cause.
As reported previously by MedWire News, the trial was stopped prematurely upon the recommendations of an independent data-monitoring committee and the JUPITER steering committee after a median follow-up of 1.9 years, at which time there had been 142 major CV events in the rosuvastatin group and 251 in the placebo group. During the study, rosuvastatin reduced LDL cholesterol by 50% and hsCRP by 37%.
Rosuvastatin treatment was associated with a significant reduction in the primary endpoint, with a hazard ratio (HR) of 0.56 (p<0.00001) and a number needed to treat (NNT) over 5 years of just 25. This NNT is lower than that associated with treating hyperlipidemia in primary prevention, Ridker noted.
Rosuvastatin also significantly reduced other endpoints, including MI (HR=0.46), stroke (HR=0.52), revascularization/unstable angina (HR=0.53), nonfatal MI, nonfatal stroke, or CV death (HR=0.53), and all-cause mortality (HR=0.80).
Importantly, rosuvastatin was consistently beneficial in all subgroups evaluated, regardless of age, gender, ethnicity, or other baseline clinical characteristics, including in patients whose sole risk factor was raised hsCRP.
The safety data were very reassuring, Ridker said. The rosuvastatin group had no increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes, as has been seen in other major statin trials.
“Not only do we confirm that apparently healthy men and women with elevated hsCRP are at high risk of CV events but we demonstrate that a simple therapy can reduce their risk of heart attack, stroke, or CV death,” Ridker said. “It appears that hsCRP predicts high risk even when cholesterol is low.”
He added that applying the JUPITER screening and treatment strategy over 5 years would expect to prevent at least 250,000 MIs, strokes, revascularizations, and CV deaths in the USA alone.
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