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| TITLE |
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Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein.
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| AUTHORS |
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Paul M Ridker, Eleanor Danielson, Francisco A H Fonseca, Jacques Genest, Antonio M. Gotto, Jr., J J Kastelein, Wolfgang Koenig, Peter Libby, Alberto J Lorenzatti, Jean G Macfadyen, Børge G Nordestgaard, James Shepherd, James T Willerson, Robert J Glynn, The JUPITER Study Group
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| PUBLICATION INFORMATION |
Journal Name: The New England Journal of Medicine
Volume: 359
Pages: 2195-2207
Date Published: 11/20/2008
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| ABSTRACT/REVIEW |
What were the researchers trying to learn in this study?
They wanted to know if generally healthy people with normal low-density lipoprotein (LDL) cholesterol but increased high-sensitivity C-reactive protein (hsCRP) would benefit from statins. High sensitivity C-reactive protein is a marker of chronic low-level inflammation, and has been associated with an increased risk for heart attack, stroke, and other cardiovascular events.
What did they find?
They found that the relative risk of heart attack was more than cut in half for people who took statins compared to those who did not take statins. The statin group was also almost 50 percent less likely to suffer a stroke or need angioplasty or bypass surgery, and they were 20 percent less likely to die during the study compared to those given placebo. Rosuvastatin (CRESTOR®), the statin used in this trial, reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%.
There were 0.77 heart attacks, strokes, artery opening procedures, or deaths from heart-related causes per 100 person years of follow-up in the rosuvastatin group. That compared to 1.36 such events per 100 person years in the untreated group. Put another way, if you followed 100 generally healthy people who were taking rosuvastatin for 1 year, less than 1 such event would occur. By contrast, among 100 similar people who were not taking statins for a year, there would have been 1.36 such events recorded.
Using the same measure of 100 person years, there would have been 0.17 heart attacks in the statin group compared to 0.37 in the comparison group. Likewise, there would have been 0.18 strokes in the statin group compared to 0.34 in the comparison group. There would have been 0.41 episodes of chest pain or procedures to open arteries (revascularizations) in the statin group compared to 0.77 in the comparison group. The data also showed that these improvements in risk of heart-related events were consistent in all subgroups evaluated.
There were 1,352 serious side effects reported in the rosuvastatin group and 1,377 in the comparison group. There were no significant differences between the two study groups with regard to muscle weakness, myopathy, newly diagnosed cancer, or disorders of the blood, immune, digestive, liver, or kidney systems. There were, however, more physician reports of diabetes in the rosuvastatin group than in the comparison group (270 compared to 216).
Although the study was initially designed to follow patients for 5 years, the study was stopped early by the independent safety monitoring board. At that time, half of the participants had been followed for 1.9 years, some of which had been followed for the full 5 years. The board recommended stopping the trial because an interim analysis had shown a clear benefit of statin therapy.
Who was studied?
A total of 17,802 people were randomly assigned to receive either rosuvastatin or a look-alike placebo. Men aged 50 years and older and women aged 60 years and older were eligible provided they had no history of heart attack, stroke, or other serious cardiovascular events. They also had to have LDL cholesterol levels less than 130 mg/dL (3.36 mmol/L), high sensitivity C-reactive protein levels of 2 mg/L or greater, and triglyceride levels less than 200 mg/dL (5.6 mmol/L) to participate.
The median age of the participants was 66, meaning half were older than that and half were younger. The median body mass index (BMI) was 28.3 and 41.4% of the participants had at least 3 of the criteria for the metabolic syndrome. The study was designed with the intent to enroll a diverse population; 6,801 of the 17,802 participants were women (38.2%) and 4,485 (25.2%) were black or Hispanic.
People were excluded from participating if they were using medication to lower their cholesterol, taking postmenopausal hormone-replacement therapy, taking medications to suppress the immune system, had evidence of liver or kidney disease, had diabetes, had uncontrolled high blood pressure, uncontrolled hypothyroidism, or had cancer other than basal-cell or squamous-cell skin cancer in the previous 5 years. Those who had inflammatory conditions such as severe arthritis, lupus, or inflammatory bowel disease were excluded as such conditions can increase hsCRP. Additionally, people were excluded if they had a recent history of alcohol or drug abuse or another medical condition that might compromise safety or the successful completion of the study.
How was the study done?
There were 17,802 men and women from 26 countries with LDL cholesterol levels of less than 130 mg/dL (3.4 mmol/L) and high-sensitivity C-reactive protein levels of 2.0 mg/L or higher randomly assigned to rosuvastatin or placebo.
Those in the rosuvastatin group received a 20 mg daily dose. The control group received a look-alike placebo. Both groups were followed for the occurrence of the combined primary end point of heart attacks (myocardial infarction), stroke, procedures to open arteries (arterial revascularization), hospitalization for unstable chest pain (unstable angina), or death from cardiovascular causes.
What did researchers know before starting this study?
Current treatment guidelines for the prevention of heart attack (myocardial infarction), stroke, and death from cardiovascular causes recommend statin therapy for patients with established vascular disease, diabetes, and high cholesterol (LDL). However, half of all heart attacks and strokes occur among apparently healthy men and women with levels of low-density lipoprotein (LDL) cholesterol that are below currently recommended thresholds for treatment.
This research group had previously shown that statin therapy reduces high-sensitivity C-reactive protein levels and that among healthy people, patients with stable coronary disease, and those with the acute coronary syndrome, the size of the benefit from statin therapy was related in part to how successful the treatment was in reducing the levels of high-sensitivity C-reactive protein.
Why did they do it?
The primary objective of the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) was to see whether treatment with rosuvastatin, 20 mg daily, as compared with placebo, would reduce the number of first major cardiovascular events.
What did the researchers say their study results mean?
The researchers reported that rosuvastatin significantly reduced the incidence of major cardiovascular events in generally healthy people with elevated C-reactive protein whose LDL cholesterol levels were in the normal range.
Editor's note: Dr. Ridker reports that he currently or in the past has received research support from Astra-Zeneca (makers of CRESTOR®), Dade-Behring and Novartis, and that he is named as a co-inventor on patents held by the Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease.
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