Comparison of High-dose Rosuvastatin Versus Low-dose Rosuvastatin Plus Ezetimibe on Carotid Plaque Inflammation in Patients With Acute Coronary Syndrome

Combination therapy of ezetimibe with a low-dose statin is occasionally used to avoid statin-related side effects in clinical practice among patients with atherosclerotic cardiovascular disease. This approach is equivalent to high-dose statin therapy to decrease LDL cholesterol level by >50%, allowing such patients to achieve LDL cholesterol target. However, it remains uncertain whether combination therapy with ezetimibe and low-dose statin verse high-dose statin monotherapy similarily suppress atherosclerotic plaque inflammation. This study is to compare high-dose rosuvastatin versus low-dose rosuvastatin plus ezetimibe on carotid plaque inflammation in patients with acute coronary syndrome using 18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET) imaging.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome; Carotid Atherosclerotic Plaque With Inflammation
• Intervention / Treatment: Drug: high-dose rosuvastatin; Drug: low-dose rosuvastatin plus ezetimibe

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Korea University Guro Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. aged ≥ 19 years
2. acute coronary syndrome, carotid artery disease (diameter stenosis 20-50%), and at least one 18FDG uptake lesion in the carotid artery (target to background ratio (TBR) ≥ 1.6) by 18FDG PET/CT imaging
3. written consent

Exclusion Criteria:

1. previous history of carotid endarterectomy or stenting
2. schedule for cardiac or major surgery within the next 6 months
3. statin or ezetimibe therapy in the past 4 weeks
4. chronic disease needed to be treated with oral, intravenous, or intraarticular steroid
5. end-stage renal disease
6. chronic liver disease
7. history of cancers within the past 3 years
8. pregnant, breast-feeding or child-bearing potential
9. expected life expectancy within 2 years

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
Active Comparator: Rosuvastatin; rosuvastatin 20 mg once a day for 6 months	Drug: high-dose rosuvastatin; rosuvastatin 20 mg once a day for 6 months
Experimental: ezetimibe/rosuvastatin; ezetimibe/rosuvastatin 10/5 mg once a day for 6 months	Drug: low-dose rosuvastatin plus ezetimibe; ezetimibe/rosuvastatin 10/5 mg once a day for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change in most-diseased segment (MDS)-tissue blood ratio (TBR) of the index vessel	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in MDS TBR	6 months
Change in whole vessel TBR within the index vessel	6 months
Change in whole vessel TBR of the aorta	6 months
Change in total cholesterol	6 months
Change in triglyceride	6 months
Change in HDL-cholesterol	6 months
Change in LDL-cholesterol	6 months
Change in high sensitive C-reactive protein	6 months

Collaborators and Investigators

• Sponsor: Yuhan Corporation

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2017
• Primary Completion (Actual): July 23, 2019
• Study Completion (Actual): July 23, 2019

Study Registration Dates

• First Submitted: August 8, 2019
• First Submitted That Met QC Criteria: August 8, 2019
• First Posted (Actual): August 14, 2019

Study Record Updates

• Last Update Posted (Actual): August 16, 2019
• Last Update Submitted That Met QC Criteria: August 13, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: positron emission tomography; rosuvastatin; fluorodeoxyglucose F18; ezetimibe/rosuvastatin; carotid plaque inflammation
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Pathological Conditions, Anatomical; Syndrome; Inflammation; Acute Coronary Syndrome; Plaque, Atherosclerotic; 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: seeCAP

Drug and device information, study documents

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