The Effect of Rosuvastatin and Olmesartan on the Progression of Coronary Atherosclerotic Disease

Study Overview
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Brief Summary
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Stains have demonstrated consistent benefits to reduce cardiovascular events in several primary and secondary prevention trials. The suppression of plaque progression or regression may be a part of mechanism of clinical benefit. The intravascular ultrasound studies demonstrated that intensive statin therapy can regress or inhibit the progression of coronary atherosclerosis. Unregulated renin-angiotensin system is important in the pathogenesis of cardiovascular disease. Angiotensin receptor antagonists (ARB) have been reported to improve clinical outcomes in patients with heart failure, left ventricular dysfunction, myocardial infarction, and high-risk patients. Several small studies showed that ARBs were effective to inhibit the progression of coronary atherosclerosis by intravascular ultrasound examination. The combined therapy with statins and ARBs may be additive or synergistic effects on the atherosclerosis regression as well as to improve endothelial dysfunction and insulin resistance in addition to lowering cholesterol levels and blood pressure when compared with either monotherapy in patients. Serial computed tomography angiography (CTA) can be utilized to assess the effect of treatment on coronary plaque morphology. In addition to the assessment of luminal stenosis, CTA also allows characterization of plaque morphology.

Official Title
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The Effect of Rosuvastatin and Olmesartan on the Progression of Coronary Atherosclerotic Disease by Smart Angioplasty Research Team: SMART-ROAD Trial

Conditions
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Coronary Syndrome

Intervention / Treatment
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* Drug: Rosuvastatin
* Drug: Olmesartan
* Drug: Combination
* Drug: Placebo of Rosuvastatin
* Drug: Placebo of Olmesartan
* Drug: Placebo of Rosuvastatin/Olmesartan(Combination)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be at 19 years 70 years of age Patients undergoing coronary CTA with coronary artery stenosis 30 70% Informed consent Appropriate CT resolution enough to measure of plaque volume Patients who are stain and renin-angiotensin system blocker naïve at least for 1 year Exclusion Criteria: Patients with>=70% luminal stenosis or requiring percutaneous coronary intervention(PCI) Severely calcifiedcoronary artery Patients who have a history of previous PCI or coronary artery bypass grafting surgery.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 70 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rosuvastatin Arm<br>Rosuvastatin 10mg in combination with placebo of Olmesartan 20mg plus placebo of Olmesartan/Rosuvastatin(Combination) 20/10mg orally once daily | Drug: Rosuvastatin<br> <br> Drug: Placebo of Olmesartan<br> <br> Drug: Placebo of Rosuvastatin/Olmesartan(Combination)<br> <br> |
| Experimental: Olmesartan Arm<br>Olmesartan 20mg in combination with placebo of Rosuvastatin 10mg plus placebo of Olmesartan/Rosuvastatin(Combination) 20/10mg orally once daily | Drug: Olmesartan<br> <br> Drug: Placebo of Rosuvastatin<br> <br> Drug: Placebo of Rosuvastatin/Olmesartan(Combination)<br> <br> |
| Experimental: Combination Arm<br>Olmesartan/Rosuvastatin(Combination) 20/10mg in combination with placebo of Rosuvastatin 10mg plus placebo of Olmesartan 20mg | Drug: Combination<br>* Rosuvastatin/Olmesartan(Combination)<br>Drug: Placebo of Rosuvastatin<br> <br> Drug: Placebo of Olmesartan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PAV(nominal change of percent atheroma volume) in the proximal to mid segments of major epicardial coronary arteries | Left main, LAD proximal to mid (from ostium to a large second diagonal branch), LCX proximal (from ostium to a large first obtuse marginal branch), RCA (from ostium to a distal bifurcation) | Over the 48weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TAV (nominal change of total atheroma volume) in the proximal to mid segments of major epicardial coronary arteries | Left main, LAD proximal to mid (from ostium to a large second diagonal branch), LCX proximal (from ostium to a large first obtuse marginal branch), RCA (from ostium to a distal bifurcation) | Over the 48weeks | 
| LAPV (nominal change of percent low attenuation plaque volume) |  | Over the 48weeks | 
| Nominal change of atheroma volume in 10 mm subsegment with greatest disease severity |  | Over the 48weeks | 
| Change in insulin resistance |  | Over the 48weeks | 
| Major adverse cardiac events |  | Over the 48weeks |