JUPITER: Low LDL and low CRP best for reducing events in primary prevention

Orlando, FL - Reducing LDL cholesterol and high-sensitivity C-reactive protein (hs-CRP) in primary-prevention patients treated with rosuvastatin (Crestor, AstraZeneca) results in better event-free survival than when neither of these targets are achieved or when LDL cholesterol alone is reduced, a new analysis shows [1].

Presenting the results of the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study during an afternoon press conference at the American College of Cardiology 2009 Scientific Sessions, investigators say that initial interventions for low-risk primary-prevention patients remains lifestyle and dietary modifications, but for those choosing drug therapy, "reductions in both LDL cholesterol and hs-CRP are indicators of the success of treatment with statin therapy."

"Our data show that patients do better when they not only lower LDL cholesterol but also lower their CRP level," Ridker told the media. "This is good news. We have a way to improve care and can consider monitoring inflammation the same way that we monitor LDL cholesterol to benefit our patients."

Dr James Stein (University of Wisconsin, Madison), who was not part of the JUPITER study, told heartwire that the message from the JUPITER analysis is straightforward but important, especially since the data challenge current treatment paradigms and make a strong case for including hs-CRP in future guidelines.

"They challenge the concept of using LDL-cholesterol values as a threshold for starting treatment and now challenge using LDL cholesterol and non-HDL cholesterol as the sole primary and secondary targets for lipid therapy," said Stein. "There are almost as many data for using hs-CRP as a target as there are for using LDL cholesterol and certainly more data for using hs-CRP than there were for LDL cholesterol when [Adult Treatment Panel] III came out."

The findings, which will be presented here during a late-breaking clinical-trials session on Monday, March 30, 2009 at 2:00 pm local time, are now published in the Lancet.

Lowering LDL cholesterol and reducing inflammation

When JUPITER was presented last November at the American Heart Association 2008 Scientific Sessions, investigators, along with other clinicians, suggested that reducing LDL cholesterol while simultaneously treating inflammation was one of the reasons treatment was successful. Other studies, including analyses of the PROVE-IT and REVERSAL trials, both of which were reported by heartwire, showed that lower CRP levels were associated with fewer cardiovascular events, independent of LDL-cholesterol levels. Data from the A to Z trial also showed that patients with acute coronary ischemia who achieved low LDL-cholesterol and CRP levels achieved the best clinical outcomes.

"The current guidelines emphasize LDL-cholesterol targets, and that is a very effective strategy," said Ridker. "But evidence has accumulated from our group and others over the past decade that suggests the benefit of statins is also related to underlying levels of inflammation, and the inflammation reduction you get with these drugs seems to be predictive of outcomes."

Still, inflammation, specifically whether or not it is necessary to lower hs-CRP levels after the initiation of statin therapy, is controversial. With this in mind, Ridker and colleagues prospectively assessed the benefits of lowering LDL cholesterol and hs-CRP in healthy men and women treated with rosuvastatin.