Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS)

Study Overview
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Brief Summary
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The purpose of this study is to compare the effects of pitavastatin and atorvastatin on coronary plaque volume in patients with acute coronary syndrome and to clarify the relationship between coronary plaque volume, serum lipids, and inflammation markers in order to determine the significance of intensive lipid lowering therapy in patients with acute coronary syndrome in Japan.

Detailed Description
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Previous mega trials have demonstrated that lipid lowering therapy with HMG-CoA reductase inhibitors (statins) reduces the incidence of major cardiovascular events by one-third, thus, the benefit of lipid lowering therapy has been substantiated. Such a benefit is significant especially for patients with coronary heart disease (CHD). The third report of the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP-III) has suggested the advantage of more intensive lipid lowering therapy with a goal of reducing LDL-C below 70 mg/dL for such patients categorized as very high risk. In Japan, Japan Atherosclerosis Society (JAS) Guidelines for Diagnosis and Treatment of Atherosclerotic Cardiovascular Diseases 2002 have recommended that an LDL-C goal for patients with coronary heart disease should be below 100 mg/dL. However, there is no satisfactory evidence yet for the need to lower LDL-C level less than the goal prescribed in Japan. Recently, research on diagnosis of coronary plaque has shown significant advances. The REVERSAL study in patients with a history of CHD, by diagnosis with intravascular ultrasound, suggested that intensive lipid lowering therapy with atorvastatin (80 mg/day) was associated with no growth of plaque (-0.4% compared to baseline), versus therapy with pravastatin (40 mg/day) which showed a slight increase (2.7%) in plaque volume over 18 months. In Japan, the ESTABLISH study, a single center study, indicated that early intensive lipid lowering therapy with atorvastatin (20 mg/day) could induce a significant reduction in plaque volume in patients with acute coronary syndrome. However, this benefit has not been verified in multicenter trials in Japan. Further, no comparative investigation into the effect of various concomitant drugs on coronary plaque has been done. Pitavastatin is a chemically synthesized statin in Japan which has been marketed since late 2003. Pitavastatin has an LDL-C lowering effect as strong as atorvastatin and also has a superior HDL-C elevating effect; meanwhile, the effect of pitavastatin on coronary plaque has not been reported.

Official Title
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Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome

Conditions
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Coronary Disease, Hypercholesterolemia

Intervention / Treatment
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* Drug: Pitavastatin
* Drug: Atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with written consent by their own volition after being provided sufficient explanation for their participation in this clinical trial Patients 20 years or older at the time of their consent Patients with hypercholesterolemia as defined by any of the following criteria: TC >= 220 mg/dL; LDL-C >= 140 mg/dL; Cholesterol-lowering treatment is necessary in accordance with the investigator's judgement when LDL-C >= 100 mg/dL or TC >= 180 mg/dL. Patients who have been diagnosed with acute coronary syndrome Patients with successful percutaneous coronary intervention (PCI) by intravascular ultrasound (IVUS) guidance Patients having coronary plaques (>= 500 µm in thickness or 20% or more in % plaque) at >= 5 mm from the previously treated area in the same branch of coronary artery Exclusion Criteria: Patients with bypass graft or in-stent restenosis at the site of PCI Patients who had received PCI on the lesion in the past where the evaluation of coronary plaque volume is planned Patients who had plaques in a non-culprit site and might receive PCI during the treatment period Patients receiving lipid-lowering drugs (statins, fibrates, probucol, nicotinic acid or cholesterol absorption inhibitors) Patients with familial hypercholesterolemia Patients with cardiogenic shock Patients receiving cyclosporine Patients with any allergy to pitavastatin or atorvastatin Patients with hepatobiliary disorders Pregnant women, women suspected of being pregnant, or lactating women Patients with renal disorders or undergoing dialysis Patients who are ineligible in the opinion of the investigator

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Pitavastatin | Drug: Pitavastatin<br>* Pitavastatin 4mg per day<br>|
| Active Comparator: 2<br>Atorvastatin | Drug: Atorvastatin<br>* Atorvastatin 20mg per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plaque volume |  | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| total cholesterol (TC) |  | one year | 
| low-density lipoprotein (LDL)-cholesterol (LDL-C) |  | one year | 
| high-density lipoprotein (HDL)-cholesterol (HDL-C) |  | one year | 
| HDL2-C |  | one year | 
| HDL3-C |  | one year | 
| remnant like particles-cholesterol (RLP-C) |  | one year | 
| small dense LDL-C |  | one year | 
| non-HDL-C |  | one year | 
| LDL-C/HDL-C |  | one year | 
| apolipoprotein AI (apoA-I) |  | one year | 
| apoB |  | one year | 
| apoE |  | one year | 
| apoB/apoA-I |  | one year | 
| malondialdehyde-modified LDL (MDA-LDL) |  | one year | 
| phospholipids |  | one year | 
| lipoprotein(a) [Lp(a)] |  | one year | 
| high-sensitivity C-reactive protein (hs-CRP) |  | one year | 
| pentraxin 3 |  | one year | 
| leukocytes |  | one year | 
| coronary plaque area at culprit region |  | one year | 
| minimal lumen diameter (MLD) and percent (%) stenosis |  | one year | 
| major adverse cardiac events (cardiac death, Q or non-Q myocardial infarction and target vessel revascularization) |  | one year | 
| number of deaths from any cause |  | one year | 
| frequency of adverse drug reactions |  | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute coronary syndrome, Hypercholesterolemia, Primary coronary intervention, Hydroxymethylglutaryl-CoA reductase inhibitors, coronary plaque, Angioplasty, Transluminal, Percutaneous Coronary, Ultrasonography, Interventional