The Pravastatin Inflammation CRP Evaluation (PRINCE): Rationale and design

Background Randomized, controlled trials demonstrate that HMG CoA reductase inhibition reduces coronary event rates in both primary and secondary prevention. In addition to reducing cholesterol levels, laboratory evidence suggests that statins also have anti-inflammatory activity, a property that may be critical for maintaining plaque stability. Recently, the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) has been shown to predict vascular risk in individuals with and without hyperlipidemia. Furthermore, in the Cholesterol and Recurrent Events (CARE) trial, the relative efficacy of pravastatin in reducing events was greatest among those with elevated levels of hs-CRP. However, the time course and magnitude of this effect in both primary and secondary prevention is controversial. Methods PRavastatin Inflammation CRP Evaluation (PRINCE) is an investigator-initiated, multicenter, community-based trial that will evaluate the effects of pravastatin on hs-CRP in vp to 1182 individuals with coronary artery disease and up to 1702 individuals without coronary artery disease. Lipid profiles and hs-CRP levels will be obtained at baseline, 12 weeks, and 24 weeks in all study participants. Patients with known coronary artery disease will receive 40 mg/d pravastatin, whereas those without coronary artery disease will be randomly assigned to receive placebo or 40 mg/d pravastatin. Conclusions The potential clinical impact of the PRINCE trial is substantial because nearly 50% of myocardial infarctions in the United States occur in persons with normal cholesterol levels, and inflammatory markers such as hs-CRP may provide a means to detect such individuals at high risk who do not currently qualify for statin therapy. The PRINCE trial will determine the time course of effect of this statin on hs-CRP and whether any observed effect on hs-CRP is independent of pravastatin-induced changes in low-density lipoprotein cholesterol.