Comparison of Rosuvastatin and Atorvastatin in Patients With Acute Coronary Syndrome
Condition: Dyslipidemia; Acute Coronary Syndromes
MeSH terms: Acute Coronary Syndrome; Dyslipidemias; Syndrome
Study type: Interventional
Phase: Phase 4

Summary: 
      This is a 3-month, randomized, parallel-group study with 2 periods, comparing the efficacy
      and the safety of rosuvastatin 20 mg versus atorvastatin 80 mg in patients with an acute
      coronary syndrome (ACS).
    

Detailed description: 
      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:

      This is a 3-month, randomized, parallel-group study with 2 periods, comparing the efficacy
      and the safety of rosuvastatin 20 mg versus atorvastatin 80 mg in patients with an acute
      coronary syndrome (ACS).

        -  The study comprises a 1st double blind, placebo controlled, period that starts at the
           admission of the patient for an ACS (clinical symptoms less than 24 hours) until
           hospital discharge (or a maximum timeline of 6 days).

        -  The 2nd double blind, double dummy, period starts at Day 0 (i.e. from the hospital
           discharge or at a maximum of 6 days after admission) and will last 3 months. After
           validation of eligibility criteria (including a 1st local assessment of CK, creatinine,
           ALT and an ECG) and the planning of a PCI between 24 hours and 4 days after admission,
           patients will be randomized into 3 groups:

             1. early started rosuvastatin 20 mg from admission until the end of the study (group 1
                - early rosuvastatin 20 mg),

             2. placebo from admission until Day O (i.e. until hospital discharge or for a maximum
                of 6 days) followed by rosuvastatin 20 mg until the end of the study (group 2 -
                late rosuvastatin 20 mg),

             3. placebo from admission until Day O (i.e. until hospital discharge or for a maximum
                of 6 days) followed by atorvastatin 80 mg until the end of the study (group 3 -
                atorvastatin 80 mg).
    

Intervention name(s): rosuvastatin; placebo; rosuvastatin; atorvastatin
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): rosuvastatin 20 mg from day 0 to (maximum) day 6; placebo 20 mg from day 0 to (maximum) day 6; rosuvastatin 20 mg from discharge until the end of the study; atorvastatin 80 mg from discharge until the end of the study
Intervention MeSH terms: Atorvastatin; Rosuvastatin Calcium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment