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)

Patients with atherosclerotic peripheral artery disease often have combined coronary artery disease or cerebral artery disease and show high rates of cardiovascular mortality and morbidities. Therefore, secondary prevention for these patients is of great clinical importance. Currently, Korean, US, and European guidelines recommend different LDL cholesterol target goals in patients with peripheral artery disease. In recent clinical trials, combination therapy of statin plus ezetimibe demonstrated improved cardiovascular outcomes compared with statin monotherapy. Thus, the purpose of the CARE-PVD study is to investigate whether the combination therapy of high intensity rosuvastatin 20 mg plus ezetimibe 10 mg can improve cardiovascular outcomes in patient with peripheral artery disease or polyvascular artery disease in comparison with rosuvastatin treat-to-target (LDL cholesterol <70 mg/dL) monotherapy.

Study Overview

• Status: Recruiting
• Conditions: Peripheral Artery Disease; Polyvascular Disease
• Intervention / Treatment: Drug: Combination therapy of high-intensity dose rosuvastatin and ezetimibe; Drug: Rosuvastatin monotherapy for treat-to-target

Detailed Description

• 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.

• Study Type: Interventional
• Enrollment (Estimated): 2462
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Young-Guk Ko, MD, PhD; Phone Number: 02)-2228-8460; Email: ygko@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine
    • Contact: Young-Guk Ko, MD, PhD; Phone Number: 02)-2228-8460; Email: ygko@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Ages 19-80

2. 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
3. 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:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rosuvastatin/ezetimibe combination therapy; Combination therapy of high-intensity dose rosuvastatin and ezetimibe	Drug: Combination therapy of high-intensity dose rosuvastatin and ezetimibe; Combination therapy of rosuvastatin 20 mg and ezetimibe 10 mg
Active Comparator: Rosuvastatin monotherapy; Rosuvastatin monotherapy for treat-to-target (LDL cholesterol < 70 mg/dL)	Drug: Rosuvastatin monotherapy for treat-to-target; Rosuvastatin monotherapy for treat-to-target (LDL cholesterol <70 mg/dL)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of Major cardiovascular event or major adverse limb event	Composite of Major cardiovascular event (MACE) or major adverse limb event (MALE) at 3-year follow-up MACE includes death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, and hospitalization for unstable angina or heart failure. MALE includes acute lower extremity ischemia, major lower extremity amputation, and revascularization of lower extremity arteries.	at 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major cardiovascular event(death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, and hospitalization for unstable angina or heart failure)	Major cardiovascular event(death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, and hospitalization for unstable angina or heart failure)	at 1, 2, and 3 years
Major adverse limb event(acute lower extremity ischemia, major lower extremity amputation, and revascularization of lower extremity arteries)	Major adverse limb event(acute lower extremity ischemia, major lower extremity amputation, and revascularization of lower extremity arteries)	at 1, 2, and 3 years
discontinuation of lipid lowering therapy	Intolerance of lipid lowering therapy	at 1, 2, and 3 years
adverse clinical events related to lipid lowering therapy	adverse clinical events related to lipid lowering therapy	at 1, 2, and 3 years
Major cardiovascular event : non-fatal myocardial infarction		at 1, 2, and 3 years
attainment of LDL cholesterol	attainment of LDL cholesterol goal	at 1, 2, and 3 years

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2024
• Primary Completion (Estimated): May 6, 2026
• Study Completion (Estimated): May 6, 2029

Study Registration Dates

• First Submitted: December 8, 2023
• First Submitted That Met QC Criteria: January 21, 2024
• First Posted (Actual): January 30, 2024

Study Record Updates

• Last Update Posted (Estimated): May 20, 2025
• Last Update Submitted That Met QC Criteria: May 14, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Peripheral artery disease; LDL cholesterol; Clinical outcomes; polyvascular disease; lipid lowering therapy
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Peripheral Arterial Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Ezetimibe
• Other Study ID Numbers: 4-2023-1212

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No