NEW ORLEANS—The much-anticipated results of the JUPITER study show that rosuvastatin (Crestor) significantly reduced the incidence of cardiovascular events in healthy people who do not have cholesterol but have elevated high-sensitivity C-reactive protein levels (test that measures inflammation). The study was presented Sunday in the late-breaking clinical trials at the American Heart Association (AHA) Scientific Sessions, and simultaneously published in the New England Journal of Medicine (NEJM).
Essentially, the results show statin use can cut the risk of cardiovascular disease by about half, even if the patient’s cholesterol is normal. In all, 18,000 patients at 1,300 healthcare facilities in 26 countries took part in the study which was sponsored by AstraZeneca, the maker of Crestor.
Lead author Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital in Boston, presented the findings of JUPITER (Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin), which found that Crestor reduced heart attacks by 54 percent in people who had normal cholesterol, but elevated levels of high-sensitivity C-reactive protein (hsCRP).
“Compared to those who received placebo, patients receiving the drug rosuvastatin also had a 48 percent reduction in stroke, a 46 percent reduction in the need for interventions to reopen blocked blood vessels and a 20 percent drop in all-cause mortality,” Ridker said.
The researchers randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and hsCRP levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily or placebo and followed them for the occurrence of the combined primary end point of MI, stroke, arterial revascularization, hospitalization for unstable angina or death from cardiovascular causes.
Overall, compared to placebo-treated participants in the trial, those given rosuvastatin had a 44 percent reduction in the primary endpoint.
Ridker noted that hospitalizations for cardiac reasons also were reduced, adding that the strategy tested in JUPITER of treating elevated hsCRP patients with statin therapy could be cost-effective and would be worth further study.
In the accompanying NEJM editorial, Mark A. Hlatky, MD, from Stanford University in California, said that the “relative risk reductions achieved with the use of statin therapy in JUPITER were clearly significant. However, absolute differences in risk are more clinically important than relative reductions in risk in deciding whether to recommend drug therapy, since the absolute benefits of treatment must be large enough to justify the associated risks and costs.” He noted that the “cost of rosuvastatin [roughly $3.45 per day] is much higher than that of generic statins.”
Ridker said the study found no increase in the number of patients with either muscle pain or cancer among those given rosuvastatin. However, they did observe a small increase in reported diabetes “as in almost all prior statin trials,” Ridker said. However, Hlatky said that “of concern are the significantly higher glycated hemoglobin levels and incidence of diabetes in the rosuvastatin group” (3 percent vs. 2.4 percent in the placebo group).
Ridker cautioned that they very low LDL levels produced by rosuvastatin, with a median 54 at 24 months, raise the question of whether other adverse effects might be seen over a longer time period, but it was “not evident” in JUPITER.
“This study demonstrated a significant reduction in heart attacks and strokes in treating this group, selected from an initially screened group of more than 89,000. However, it was not designed to answer the question of whether the impact on risk was due to reduction in inflammation [marked by hs-CRP] or a reduction in LDL,” said Timothy Gardner, MD, president of AHA. “Thus, the findings presented today cannot determine whether lowering cholesterol, reducing inflammation or a combination of both is responsible for the effects seen in this paper.”