Efficacy and Safety of FDC in High Risk Patients With Primary Hypercholesterolemia or Mixed Dyslipidemia (LANCE)

• Changes in HDL, triglycerides and apolipoprotein B levels [ Time Frame: Baseline compared to the end of 9 weeks of treatment ] [ Designated as safety issue: No ]
• Safety descriptive about occurence of adverse events, evaluation of results of general physical examination. [ Time Frame: Will be evaluated during whole study, at the baseline and after 9 weeks of treatment ] [ Designated as safety issue: Yes ]
  Collection of safety data throughout the whole study period

The purpose of this study is to determine the non-inferiority between two different FDC, measuring LDL-Cholesterol levels, in high risk patients by NCEP-ATP III, with primary hypercholesterolemia or mixed dyslipidemia.

• Hypercholesterolemia
• Dyslipidemia

• Drug: Rosuvastatin + Ezetimibe
  Tables containing: Rosuvastatin 10 mg + Ezetimibe 10 mg and Rosuvastatin 20 mg + Ezetimibe 10 mg, according with titration.
• Drug: Simvastatin + Ezetimibe
  Tables containing: Simvastatin 20 mg + Ezetimibe 10 mg and Simvastatin 40 mg + Ezetimibe 10 mg, according with titration.

• Experimental: Group 01
  Rosuvastatin 10 mg + Ezetimibe 10 mg and Rosuvastatin 20 mg + Ezetimibe 10 mg, according with titration.
  Intervention: Drug: Rosuvastatin + Ezetimibe
• Active Comparator: Group 02
  Simvastatin 20 mg + Ezetimibe 10 mg and Simvastatin 40 mg + Ezetimibe 10 mg, according with titration.
  Intervention: Drug: Simvastatin + Ezetimibe

Inclusion Criteria:

• Patients of both sexes, aged between 18 and 70 years, remaining the feasibility of a legal guardian in accordance with need, able to understand and provide written informed consent and able to allow compliance at the treatment and the requirements of the protocol;
• Confirmed diagnosis of primary hypercholesterolemia;
• Confirmed diagnosis of mixed dyslipidemia;
• Liver transaminases ≤ 2 x upper limit of normal with no active liver disease;
• Creatinine kinase (CK) less or equal the upper limit of normality;
• Patients should not have clinically significant comorbidities, which may interfere in the evaluation of study;
• Patients who is willing to maintain a cholesterol-lowering diet throughout the study;
• Patients need to agree in discontinue the previous medication for hypercholesterolemia treatment and switch to the study medication.
• Patients with primary hypercholesterolemia who have LDL-C > 160 mg/dl and < 220 mg/dl; and triglyceride (TG) concentration < 350 mg/dl

Exclusion Criteria:

• Heart failure class III or IV (NYHA);
• Blood dyscrasia;
• Unstable angina pectoris;
• Myocardial infarction in the last 3 months;
• Planning for CABG, peripheral or carotid percutaneous intervention for the next 90 days;
• Renal insufficiency (estimated GFR < 30 ml/min/m2);
• Liver transaminases > 2 x upper limit of normal;
• Asian patients or kinship asian;
• History of alcoholism or drug abuse;
• Patients with comorbidities that hinder the interpretation of results or contraindicate the lipid-lowering therapy [uncompensated hypothyroidism (TSH > 8 mUI/mL); uncompensated diabetes (HbA1c > 8%); active hepatic disease; antiretroviral therapy, neoplasm (except for adequately treated squamous cell skin cancer within the past 5 years), concomitant immunosuppressive therapy (transplanted and rheumatic disease).
• Non-compensated hypertension (BP ≥ 160/100 mm Hg);
• Women of childbearing age who had tested positive for pregnancy, or who do not use acceptable contraceptive method, or do not agree to practice reliable contraception during the study;
• Woman in pregnancy or lactation period;
• Hypersensibility to ezetimibe or rosuvastatin, or any component of these medications;
• Participation in last one year of clinical protocols, unless it can be direct benefit to patient;
• Any finding of clinical observation (anamnesis and physical exam) laboratory abnormality (eg, blood glucose, blood count), disease (for example, liver, cardiovascular system, lung) or therapy that, in opinion of the investigator, may endanger the subject or interfere with the endpoints of study.