Rosuvastatin Reduces Heart Attack, Stroke, Total Mortality

Ruzanna Harutyunyan's picture

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).

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".