The Pravastatin Inflammation/CRP Evaluation (PRINCE) Paul M. Ridker Brigham and Women's Hospital, Boston, Massachusetts, USA Physicians are paying more attention each day to the pivotal role of inflammation in cardiovascular disease, and the plasma level of C-reactive protein, an indicator of inflammation, has been identified as a predictor of cardiovascular risk. The results of this study describe the ability of pravastatin to reduce plasma levels of C-reactive protein independently of the drugﾕs lipid-lowering effects. The plasma level of C-reactive protein, an indicator of inflammation, has been identified as a risk factor for cardiovascular disease in many studies, and this relation has been demonstrated consistently in all age groups and ethnic groups. There is a great deal of evidence for the importance of inflammation in the special situation of atherosclerotic plaque instability and rupture leading to acute thrombosis and coronary artery occlusion. The Womenﾕs Health Initiative study linked the risks associated with C-reactive protein and with elevated serum lipids. In the CARE trial, randomization to the pravastatin treatment group was found to be associated with a trend toward lower C-reactive protein levels. However, those data were retrospective and the trial was not designed to evaluate the possibility of an effect of pravastatin in decreasing inflammation. Dr. Ridker said: "Therefore, we designed the Pravastatin Inflammation/CRP Evaluation, or PRINCE trial, as a prospective study to investigate this possible effect and to understand more about its time course and possible relationship to the patientﾕs LDL cholesterol level." A total of 2,237 patients were enrolled, mostly in primary care settings, and randomized to receive either pravastatin 40 mg per day or placebo for 24 weeks. There were two cohorts in the active treatment group: a secondary prevention cohort and a primary prevention cohort. As would be expected, pravastatin reduced total cholesterol levels by 18%. It also reduced C-reactive protein levels by 13% (p < .001). These results were consistent in all subgroups. There were no changes from baseline in total cholesterol or C-reactive protein among patients in the placebo group. Regarding the time course of the pravastatin effect, similar results were seen at the midpoint of the study, 12 weeks after initiation of therapy. Dr. Ridker commented on the relation between the observations: "The effect of pravastatin on C-reactive protein levels was not associated with the patientﾕs baseline LDL levels or the change in LDL. Therefore, this effect appears to be independent of the drugﾕs lipid-lowering effects. We cannot determine without additional study if there is any correlation between this effect and the beneficial clinical effects of pravastatin. Also, we have no way of knowing at this point if this is a specific drug effect or a class effect of the statins. As inflammation is so important in cardiovascular disease, and statins are such an important component of pharmacotherapy for people with cardiovascular disease, we are certainly going to investigate this effect further in the future." Reporter: Andre Weinberger, MD Copyright 2000-2013 by HESCO International, Ltd. All rights reserved.