Rosuvastatin Dramatically Reduces Heart Attack, Stroke and Total Mortality Among Men, Women with Low Cholesterol but Elevated C-Reactive Protein Level
hsCRP Important for Effective Heart Disease Detection and Treatment
Boston, MA – Until now, there has been no proven method to detect and prevent the many heart attacks and strokes that occur in patients with normal or low cholesterol levels. In the landmark JUPITER trial of 17,802 patients, researchers from Brigham and Women’s Hospital (BWH) report that rosuvastatin reduces by nearly fifty percent the risk of heart attack, stroke, and cardiovascular death among apparently healthy men and women participating in the trial who had low levels of cholesterol but were nonetheless at high risk for vascular disease due to increased levels of a simple blood test for the inflammatory biomarker hsCRP (high sensitivity C-reactive protein). These findings appear in the November 20, 2008 issue of the New England Journal of Medicine and will be presented November 9th at the 2008 Scientific Sessions of the American Heart Association. The New England Journal of Medicine will also publish the findings online November 9, 2008.
In the JUPITER trial which focused on low cholesterol/high hsCRP patients, a daily regimen of rosuvastatin was associated with a 54 percent reduction in heart attack, a 48 percent reduction in stroke, a 46 percent reduction in need for angioplasty or bypass surgery, and a 20 percent reduction in all-cause mortality compared to participants who were given a placebo. These effects are nearly twice as large as what doctors expect when using statin therapy among patients with high cholesterol, demonstrating the importance of elevated hsCRP as a major risk factor for cardiovascular disease. Among trial participants with elevated hsCRP but no other risk factors, rosuvastatin reduced cardiovascular events by 37 percent. There was no difference between treatment groups for major adverse events, including cancer or myopathy. As in almost all prior statin trials, there was a small increase in reported diabetes.
Dr Robert Glynn, the academic study statistician, estimated that approximately 250,000 heart attacks, strokes, revascularization procedures, or cardiac deaths could be avoided in the US alone if the strategy tested in JUPITER was applied over a five year period.
“Our results are relevant for patient care and the prevention of heart attack and stroke,” said Paul Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital and lead author of the study. “Physicians can no longer assume that patients are at low risk for heart disease simply because they have low cholesterol. We have confirmed that patients with increased hsCRP are at high risk even if cholesterol levels are low, and we now have evidence that a simple and safe therapy cuts that risk and saves lives.”
The JUPITER trial results also demonstrate for the first time that statin therapy is highly effective in the prevention of heart disease among women and minority patients, groups that typically have been excluded or understudied in prior trials. For example, rosuvastatin reduced the risk of cardiovascular events by 46 percent in women compared to 42 percent in men.
Started in 2003, JUPITER (the Justification for Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) was designed to test whether rosuvastatin, taken at 20mg daily compared to placebo, could reduce the risk of cardiovascular events among apparently healthy men and women who had LDL cholesterol levels below 130mg/dL who were nonetheless at silent risk due to increased levels of inflammation as measured by a simple blood test known as high sensitivity C-reactive protein (hsCRP).
Prior work had established that patients with increased hsCRP were at high risk for heart disease despite lacking other conventional risk factors, and that statins lower hsCRP levels, indicating anti-inflammatory as well as cholesterol lowering effects. Until JUPITER, whether or not statin treatment would be effective in reducing cardiac events among these patients had been uncertain.
“The JUPITER trial data are paradigm shifting and a win-win for patients and for health care providers” said Dr. Antonio Gotto, Dean of the Weill-Cornell Medical College in New York. “We should regularly measure hsCRP along with lipids when we determine cardiovascular risk.”
“For the cardiology world, discovering a major new risk factor as well as an effective treatment is like hitting a walk-off home run to win the World Series,” said Dr. Eugene Braunwald, a renowned cardiologist also at Brigham and Women’s Hospital.
The strategy of screening for hsCRP and treating those at high risk is likely to be cost-saving since rates of hospital admission and the need for expensive angioplasty and coronary artery bypass surgery were also reduced by nearly 50 percent among trial participants receiving rosuvastatin.
Participants in JUPITER had cholesterol levels widely considered optimal by most physicians; the average LDL or “bad” cholesterol was just above 100 mg/dL and the average HDL or “good” cholesterol was nearly 50 mg/dL. Nonetheless, event rates in the trial were high because all participants had elevated levels of hsCRP.
“JUPITER should dramatically change prevention guidelines” said Dr. James Willerson, Director of the Texas Heart Institute in Houston. “The bottom line here is simple – if your hsCRP is high, you should be on statin therapy regardless of your cholesterol level. This is an approach we can start using tomorrow”.
Led by Dr. Ridker of BWH, JUPITER was a randomized, double-blind, placebo-controlled trial conducted by investigators in 26 countries and overseen by an academic statistician (Robert Glynn, PhD, Harvard University, USA) and an independent Data and Safety Monitoring Board (chaired by Professor Rory Collins, Oxford University, UK). The study was funded by AstraZeneca, US who had no access to unblinded trial data and played no role in analysis or interpretation of the study data nor in manuscript preparation. Dr. Ridker is listed as a co-inventor on patents held by BWH that relate to the use of inflammatory biomarkers in cardiovascular disease that have been licensed to AstraZeneca and Siemens Healthcare Diagnostics in the therapeutic and diagnostics field respectively.
Brigham and Women's Hospital (BWH) is a 777-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare, an integrated health care delivery network. In July of 2008, the hospital opened the Carl J. and Ruth Shapiro Cardiovascular Center, the most advanced center of its kind. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives and its dedication to educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving more than 860 physician-investigators and renowned biomedical scientists and faculty supported by more than $416 M in funding. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative. For more information about BWH, please visit www.brighamandwomens.org.
Send
Feedback to: 
