Vascular Effects of Ezetimibe/Simvastatin and Simvastatin on Atherosclerosis

Study Design:

A single-blind controlled trial with two arms will be conducted at National Chen-Kung University Hospital (NCKUH). We will screen subjects with stable atherosclerosis to complete enrollment of 40 subjects in the study (see inclusion and exclusion criteria section below). A central pharmacist at NCKUH will randomize the patients to 40mg or Simvastatin (n=20) or 10mg/10mg of Ezetimibe/Simvastatin (n=20) for 28 days. If the patient is already on a statin a two-week washout period will be 2 weeks prior to trial initiation.

Primary Outcomes and measurement:

The primary outcomes are the mean changes in the Rho-kinase expression and activity in leukocytes in response to 40mg or Simvastatin (n=20) or 10mg/10mg of Ezetimibe/Simvastatin (n=20) over 28 days.

Secondary Outcomes and measurement:

The secondary outcomes are the correlation between the mean changes in Rho-kinase expression and activity in leukocytes and vascular tissue with the mean changes in LDL-C, hsCRP, and BAFMD, as well as its relation with clinical characteristics.

Subjects:

Participants will be recruited from the ambulatory clinics at the NCKUH Clinic.

Inclusion criteria

• Male or female subjects aged 40 to 80 years
• Documented stable atherosclerosis by angiography or vascular ultrasound (more that 20% luminal narrowing), peripheral arterial disease or type 2 diabetes mellitus (coronary heart disease (CHD) risk equivalent - Adult Treatment Program (ATP)-III guidelines)
• LDL-cholesterol >100mg/dL (indication to treat with statin)
• Written informed consent
• Primary care physician authorization letter to participate in the study.

Exclusion criteria

• Inability to give consent
• Pre-menopausal women
• Current use of antibiotics, anti-inflammatory or immunosuppressant drugs
• History of LFT >2 times the upper normal limit
• History of myopathy / myositis or CPK > 10 times the upper normal limit
• CPK above normal limits at study onset
• Any evidence of inflammatory, infectious or neoplastic disease
• History of CABG, PCI or acute ischemic syndrome in the preceding 3 months.

Inclusion criteria

• Inclusion Criteria:

• Male or female subjects aged 40 to 80 years
• Documented stable atherosclerosis by angiography or vascular ultrasound (more that 20% luminal narrowing), peripheral arterial disease or type 2 diabetes mellitus (coronary heart disease (CHD) risk equivalent - Adult Treatment Program (ATP)-III guidelines)
• LDL-cholesterol >100mg/dL (indication to treat with statin)
• Written informed consent
• Primary care physician authorization letter to participate in the study.
• Exclusion criteria:

• Inability to give consent
• Pre-menopausal women
• Current use of antibiotics, anti-inflammatory or immunosuppressant drugs
• History of LFT >2 times the upper normal limit
• History of myopathy / myositis or CPK > 10 times the upper normal limit
• CPK above normal limits at study onset
• Any evidence of inflammatory, infectious or neoplastic disease
• History of CABG, PCI or acute ischemic syndrome in the preceding 3 months.