Effects of Combined Therapy With Statin Plus Fenofibrate on Coronary Atherosclerotic Plaque Compared With Statin Alone

Study Overview
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Brief Summary
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The purpose of this study is to determine effects of combination therapy with rosuvastatin and fenofibrate on atheromatous plaques and its tissue characteristics of de novo coronary lesions with intermediate stenosis in patient with coronary artery disease, compared with rosuvastatin alone therapy.

Detailed Description
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Cardiovascular disease remains the leading cause of morbidity and mortality worldwide. In the past few decades, optimal pharmacological therapies with statins targeting LDL-cholesterol substantially reduce the risks of cardiovascular disease. However, the residual cardiovascular risk is still high, requiring need for additional preventive therapies to achieve even greater risk reduction. Recent meta-analysis demonstrated fibrates can reduce the risk of coronary events and might have a role in patients with high cardiovascular risks or combined dyslipidemia. Likewise, fenofibrate had a possible benefit for patients with high triglyceride level and low HDL-cholesterol level in the post-hoc analysis of ACCORD or FIELD trials. Thus, investigators tried to determine effects of combination therapy with rosuvastatin and fenofibrate on atheromatous plaques and its tissue characteristics of de novo coronary lesions with intermediate stenosis in patient with coronary artery disease, compared with rosuvastatin alone therapy.

Official Title
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The Comparative Analysis of the Effects on Plaque Volume and Tissue Characteristics Between Combined Therapy With STAatin Plus FENOfibrate and Statin Alone in Mild to Moderate, Non- Intervened Coronary Artery Stenosis (STAFENO Trial)

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Rosuvastatin and fenofibrate
* Drug: Rosuvastatin alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with coronary artery disease who were 20 years of age or older and needed coronary angiography Intermediate coronary artery stenosis (diameter stenosis ≥30% to ≤60% by visual estimation, diameter ≥2.0 mm to ≤4.0 mm, de novo lesion in native coronary artery) in which virtual histology-intravascular ultrasound (VH-IVUS) could be feasible Combined dyslipidemia Stain-naive patients - LDL-cholesterol ≥70 mg/dL and non-HDL-cholesterol ≥130 mg/dL Patients taking statin within 2 weeks - LDL-cholesterol < 100 mg/dL and non-HDL-cholesterol ≥100 mg/dL Patients who gave written informed consent Exclusion Criteria: Diabetic patients Cardiogenic shock Heart failure with symptoms of New York Heart Association class III/IV or left ventricular ejection fraction <35% Renal dysfunction (creatinine level ≥1.7 mg/dL or dependence of dialysis Hepatic dysfunction (transaminase level > 3 times of normal within limit) Pregnancy or breast-feeding women Familial hypercholesterolemia Hypertriglyceridemia (triglyceride level >500 mg/dL)

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rosuvastatin and fenofibrate<br>Combination therapy: rosuvastatin 10 mg and fenofibrate 160 mg per day | Drug: Rosuvastatin and fenofibrate<br>* Combination therapy: rosuvastatin 10 mg and fenofibrate 160 mg per day<br>* Other names: Combination therapy with rosuvastatin and fenofibrate;|
| Active Comparator: Rosuvastatin alone<br>Rosuvastatin 10 mg per day | Drug: Rosuvastatin alone<br>* Rosuvastatin 10mg per day<br>* Other names: Rosuvastatin alone therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent and Absolute changes of Necrotic Core volume in non-culprit intermediate lesions | Percent and Absolute changes of Necrotic Core volume in non-culprit intermediate lesions by VH-IVUS | After 12±2 months treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent and Absolute changes of area of necrotic core, dense calcium, fibrous plaque in non-culprit intermediate lesions | Percent and Absolute changes of area of necrotic core, dense calcium, fibrous plaque in non-culprit intermediate lesions by VH-IVUS | After 12±2 months treatment | 
| Presence of thin-cap fibroatheroma | change of plaque phenotype by VH-IVUS | After 12±2 months treatment | 
| Absolute and percent changes of volume/area of external elastic membrane, lumen and plaque volume | Absolute and percent changes of volume/area of external elastic membrane, lumen and plaque volume by VH-IVUS | After 12±2 months treatment | 
| Remodeling index | Remodeling index by VH-IVUS | After 12±2 months treatment | 
| Major adverse cardiovascular events (MACE) | The composites of all-cause death, non-fatal myocardial infarction, stroke, culprit lesion revascularization, or non-culprit lesion revascularization | After 12 months treatment | 
| Adverse drug events | Adverse drug events related by study drugs | After 12±2 months treatment | 
| Creatine phosphokinase | measurement of muscular side effects related by study drugs | After 12±2 months treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atherosclerotic plaque, Virtual histology intravascular ultrasound, Plaque composition, Rosuvastatin, Fenofibrate, Coronary artery disease