Effect of Atorvastatin on Fractional Flow Reserve in Coronary Artery Disease

Study Overview
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Brief Summary
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Natural course of intermediate coronary artery disease (CAD) is very important to predict the prognosis of the patient with such disease. Several studies have well demonstrated the beneficial effect of lipid-lowering therapy on the progression of CAD with the modification of lipid profiles. This effect can be also explained by intravascular ultrasound (IVUS) or optical coherence tomography. However, the effect of plaque modification on coronary physiology has been rarely evaluated. This research is to evaluate the change of intermediate or nonculprit coronary lesion on lipid-lowering therapy via IVUS(optional) and FFR.

Detailed Description
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The patients who have intermediate CAD (30-80% diameter stenosis by visual estimation) with FFR≥0.80, or nonculprit coronary artery disease with FFR≥0.8 after culprit coronary artery disease intervention will be enrolled. FFR, IVUS(optional) and index of microcirculatory resistance (IMR) should be performed simultaneously. Atorvastatin 20mg is a starting dose, then up-titration will be done twice within each 4 6weeks until LDL target goal (① LDL<70mg/dl, or ② statin naive: >50% reduction from baseline LDL, current statin user: >30% reduction from baseline LDL). First titration will be atorvastatin 40mg, second will be atorvastatin 80mg. If patients have any adverse effect on atorvastatin, the dose of atorvastatin can be adjusted by investigator's decision. Official clinical follow-up except visit for statin dose titration will occur at 1, 12 months after index procedure. Follow-up coronary angiography, FFR,IMR,and IVUS(optional) will be performed 12 months after index procedure.

Official Title
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Phase 3 Study of Effect of ATorvastatin on Fractional Flow Reserve in Coronary Artery Disease

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient > 18 years of age and willing to participate patients who have stable intermediate CAD(30-80% diameter stenosis by visual estimation) on angiography with FFR≥0.8,or who have nonculprit CAD which is not planned revascularization Signed written Informed Consent Exclusion Criteria: Patients who are in cardiogenic shock Patients with LVEF<35% Patients with left main disease, restenotic, bypass grafted lesions Patients with platelet count < 100,000 cell/mm3 Patients who have co-morbidity which reduces life expectancy to one year Patients who have a history of stroke or transient ischemic attack within 6 months Patients who are planned discontinuation of medication due to surgery Patients with known adverse reaction to HMG CO-A reductase therapy (statins) Patients with liver disease (elevation of AST or ALT more than 2 times) Patient with creatinine > 2.0 mg/dL Pregnant women and women of childbearing potential who intend to have children during the duration of the trial Patients who consistently must take drugs affecting lipid levels in blood except the investigational product

Ages Eligible for Study
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Minimum Age: 19 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atorvastatin<br>Atorvastatin (Lipitor) will be prescribed with 20mg,40mg,or 80mg by the unit of 28 tablets upon the result of lipid profile. Besides Clinical and lab test, follow-up CAG, IVUS(optional) and FFR will be performed in 12 months. | Drug: Atorvastatin<br>* Lipitor dose titration will be followed by the result of LDL lab test until it meets the target level of LDL. IVUS(optional) and FFR during follow up CAG in 12 months will be measured to evaluate the effect of lipitor.<br>* Other names: lipitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes of FFR between baseline and 12months follow-up | changes of FFR(fractional flow reserve) baseline and 12month foloow-up | up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of FFR according to the degree of decreased LDL | Change of FFR according to the degree of decreased LDL | up to 1 year | 
| Change of % plaque volume, total atheroma volume & plaque compositions in lesion of interest | Change of % plaque volume, total atheroma volume & plaque compositions in lesion of interest | up to 1 year | 
| Change of IMR | Change of IMR(index of microcirculatory resistance) | up to 1 year | 
| Death including cardiac and noncardiac | Death including cardiac and noncardiac | up to 1 year | 
| Myocardial infarction | Myocardial infarction | up to 1 year | 
| Target lesion and vessel revascularization rate | Target lesion and vessel revascularization rate | up to 1 year | 
| CVA: hemorrhage and infarction | CVA(cerebrovascular accident): hemorrhage and infarction | up to 1 year | 
| side effect of statin : liver and muscle enzyme | side effect of statin : liver and muscle enzyme | up to 1 year |