The JUPITER trial causes a stir
The JUPITER trial causes a stir
Elevated high-sensitivity C-reactive protein (CRP) may help identify otherwise healthy patients with normal cholesterol levels who will benefit from statin therapy, according to the JUPITER trial published in November. Researchers randomized nearly 18,000 healthy men and women with normal cholesterol levels (LDL < 130 mg/dL) with CRP levels of 2.0 mg/L or greater to rosuvastatin (Crestor®) 20 mg daily or placebo. The combined primary endpoint was myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular cause. The trial was stopped early at 1.9 years when the rate of the primary endpoint was found to be 0.77 per 100 person-years in the treatment group vs 1.36 per 100 person-years in the placebo (HR 0.56; 95% CI, 0.46-0.69; P < 0.00001). Overall, the rate of events was low in both groups: 142 of 8901 in the treatment group vs 251 of 8901 in the placebo group. The individual endpoints of myocardial infarction, stroke, and revascularization or unstable angina were all reduced by approximately 50% in the rosuvastatin group, LDL cholesterol levels were decreased by 50%, and CRP levels were decreased 37%. There was not a significant increase in myopathy or cancer in the treatment group, but there was a higher incidence of physician-reported diabetes. The authors conclude that in apparently healthy persons without hyperlipidemia but with elevated CRPs, rosuvastatin significantly reduced the incidence of major cardiovascular events (N Engl J Med 2008;359:2195-2207).
In an accompanying editorial, Mark Hlatky, MD, Stanford University School of Medicine, points out that although the relative risk reductions in the JUPITER trial were clearly significant, the absolute difference in risk was less impressive with 120 participants treated for 1.9 years to prevent one event. It is also difficult to know the role of CRP in risk stratification since patients with normal CRP levels were not treated and it is possible that lowering cholesterol with statins may benefit even those with low CRP levels. CRP may have a role in deciding whether to treat patients with intermediate risk, but it may be too early to use it to recommend treatment for those at low risk. Hlatky writes that "guidelines for primary prevention will surely be reassessed on the basis of the JUPITER results, but the appropriate size of the orbit of statin therapy depends on the balance between the benefits of treatment and long-term safety and cost" (N Engl J Med 2008;359:2280-2282). It is safe to say that JUPITER has been the subject of many lively discussions in hospital lunchrooms across the country. Whether the benefit of rosuva-statin can be generalized to all statins, whether CRP should be a standard part of yearly blood panels for adults patients, and whether everyone with an elevated CRP should be offered treatment with a statin are all questions that are being hotly debated and will need further evaluation.