Comparison of the Effect Noted in The Apo/Apo-1 Ratio Using Rosuvastatin and Atorvastatin in Patients With acUte Coronary Syndrome CENTAURUS Study

Patients with ACS (acute coronary syndrome) constitute a high-risk population with unstable coronary disease (CHD) that differs from stable CHD primarily in short term prognosis (prediction of outcome). The 1-year rate of death or non-fatal MI (myocardial infarction or heart attack) was 13% in patients with ACS in a recent controlled study (FRISC II 1999), compared with less than 2% in patients with stable CHD (SAPAT 1992). Thus, despite substantial progress in the treatment of ACS with antiplatelet and anti-thrombotic medications (blood thinners), additional therapies are needed to reduce the additional risk associated with unstable CHD. Current guidelines (NCEP 2001) recommend that patients admitted with a major coronary event (MI or ACS) should be considered for treatment with a statin on discharge from the hospital.

Cited advantages of this approach are patient motivation to start therapy at that time and prevention of a "treatment gap" due to inconsistent outpatient follow-up. A previously randomized controlled study of statin therapy in ACS patients (MIRACL study), showed that aggressive cholesterol lowering with atorvastatin 80 mg between 24 and 96 hours after hospital admission in patients with ACS resulted in reduced incidence of recurrent CHD events at 16 weeks. However, the study excluded patients who underwent revascularization (PCI). Thus the study enrolled only a subset of the ACS population.

There is also emerging data from clinical studies supporting the anti-inflammatory actions of statins. One recent randomized controlled study demonstrated that statins decrease the levels of CRP, considered to be a marker of intra-arterial inflammation and a predictor of recurrent adverse cardiovascular events. The relative levels of various lipid measurements, such as LDL-C, triglycerides and HDL-C probably influence the inflammatory and thrombotic (blood clotting) properties, but the exact relationship is not clear. The anti-inflammatory and antithrombotic properties of different statins are likely related to their impact on the lipid profile and their different pleiotropic properties (producing more than one genetic effect).

The present study is designed to compare the effects of rosuvastatin 20 mg versus atorvastatin 80 mg started at maximum 6 days after an ACS to lipid profile (blood cholesterol). Additionally, the hypothesis of beneficial effect on inflammatory markers compared with statins started later will be tested.

c) Summary of study design: