Randomized Comparison of Efficacy and Safety of High-intensity Rosuvastatin/Ezetimibe Combination Versus Treat-to-target Rosuvastatin Monotherapy for Patients With Peripheral Artery or Polyvascular Disease (CARE-PVD Trial)

• A multicenter prospective randomized controlled clinical trial
• A total of 2462 subjects with cperipheral artery disease or polyvascular disease will be included according to inclusion and exclusion criteria.
• Patients will be randomized in a 1:1 manner into the rosuvastatin/ezetimibe combination therapy group or rosuvastatin monotherapy group. • The randomization will be startified by previous use of statin and presence of diabetes mellitus. • In the rosuvastatin/ezetimibe combination therapy group, rosuvastatin 20 mg plus ezetimibe 10 mg will be administered. • In the rosuvastatin monotherapy group, rosuvastatin will be administered and the dose of rosuvastatin will be adjusted to attain the target LDL cholesterol level < 70 mg/dL.
• Patients will be followed clinically for 3years.
• The primary endpoint is defined as the composite of Major cardiovascular event (MACE) or major adverse limb event (MALE) at 3-year follow-up.

Inclusion criteria

• Ages 19-80
• Patient with arteriosclerotic lower extremity artery disease or multivessel disease 1) Arteriosclerotic lower extremity artery disease: If any of the following applies

• Ankle-brachial index <0.85 with symptoms of intermittent claudication
• Lower extremity artery stenosis of more than 50% on imaging tests
• History of receiving interventional or surgical treatment for lower extremity artery disease) 2) Arteriosclerotic multivessel disease: When at least two of the following diseases exist even if there is no lower extremity artery disease
• Coronary artery disease
• History of carotid artery stenosis (more than 50%) or ischemic stroke/transient cerebral ischemia event
• degenerative thoracic (maximum diameter >4 cm) or abdominal (maximum diameter >3cm) aortic aneurysm
• Patients on medication for dyslipidemia or patients with LDL cholesterol level higher than the target level for peripheral arterial disease (≥70 mg/dL) and not on lipid lowering medication

Exclusion criteria

• Chronic limb threatening ischemia (Rutherford 4~6)
• History of acute coronary syndrome or stroke/TIA or lower extremity amputation within 6 months
• Acute liver disease or persistent unexplained elevation of serum AST or ALT more than twice the upper limit of normal
• Severe renal dysfunction (eGFR <30 mL/min/1.73m2) or dependancy on dialysis
• History of allergic or hypersensitivity reaction to statin or ezetimibe or side effects requiring discontinuation of lipid lowering therapy
• Solid organ transplant recipients
• Pregnant women, potentially pregnant or lactating women
• Life expectancy of less than 3 years
• When follow-up for more than 1 year is not possible
• Inability to understand or read the consent form