AstraZeneca's Crestor (rosuvastatin) significantly reduced the risk of cardiovascular events and related deaths by 44 percent, compared to placebo, in people with normal cholesterol levels who had elevated levels of C-reactive protein (CRP), according to results from the JUPITER study presented at the American Heart Association Scientific Sessions.

 

Steven Nissen of the Cleveland Clinic said "this may be the most important trial we've seen in a decade." In the study, around 17 800 people who had low-to-normal LDL cholesterol, but who were identified as being at increased cardiovascular risk due to elevated high-sensitivity CRP, received either Crestor or placebo. Findings showed that those who took Crestor had a 47-percent reduction in the combined risk of stroke, heart attack or cardiovascular death compared with those who took placebo. The data also indicated that total mortality in the Crestor group was reduced by 20 percent versus the placebo group, and that there was a median 50-percent drop in LDL cholesterol in those who took AstraZeneca's drug.

Lead study investigator Paul Ridker remarked that the observed benefits "are approximately twice as large as what doctors expect when you use statins in patients with [high cholesterol]." The president of the American College of Cardiology, Douglas Weaver, noted that the news "takes prevention to a whole new level, because it applies to patients who we now wouldn't have any evidence to treat."

Nissen added that the findings could change medical practice, while the head of the National Heart, Lung and Blood Institute, Elizabeth Nabel, said "it's at a minimum an extremely important study and has the potential to be a landmark study." She explained that an expert panel will review the results and will draft guidelines for how and when routine tests for CRP as predictors of heart attack and stroke should be used.

Meanwhile, Mark Hlatky suggested in an editorial in the New England Journal of Medicine that the researchers need to extend the testing to other statins, including generics. He also noted that the JUPITER findings did not indicate what level of CRP should be the threshold for treatment, and he stated that the study did not answer questions about the potential risks of giving statins to people who are in generally good health.

Separately, Scott Grundy of the University of Texas Southwest Medical Center added that there are still questions about whether the benefits seen in the Crestor group came from lowering CRP or lowering LDL cholesterol. He also explained that CRP levels can fluctuate due to short-term infections unrelated to chronic inflammation.

AstraZeneca reiterated that it intends to file the JUPITER data for Crestor with the FDA in the first half of 2009. The cholesterol-lowering drug is not currently approved to prevent cardiovascular events, the drugmaker stated.