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

Phase 4
Completed
Conditions
Coronary Disease
Hypercholesterolemia
Interventions
Registration Number
NCT00242944
Lead Sponsor
Kyoto University
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
307
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
2AtorvastatinAtorvastatin
1PitavastatinPitavastatin
Primary Outcome Measures
NameTimeMethod
plaque volumeone year
Secondary Outcome Measures
NameTimeMethod
apoEone year
total cholesterol (TC)one year
HDL2-Cone year
HDL3-Cone year
apoBone year
low-density lipoprotein (LDL)-cholesterol (LDL-C)one year
malondialdehyde-modified LDL (MDA-LDL)one year
high-density lipoprotein (HDL)-cholesterol (HDL-C)one year
LDL-C/HDL-Cone year
high-sensitivity C-reactive protein (hs-CRP)one year
minimal lumen diameter (MLD) and percent (%) stenosisone year
major adverse cardiac events (cardiac death, Q or non-Q myocardial infarction and target vessel revascularization)one year
apolipoprotein AI (apoA-I)one year
frequency of adverse drug reactionsone year
remnant like particles-cholesterol (RLP-C)one year
non-HDL-Cone year
pentraxin 3one year
apoB/apoA-Ione year
phospholipidsone year
coronary plaque area at culprit regionone year
lipoprotein(a) [Lp(a)]one year
leukocytesone year
number of deaths from any causeone year
small dense LDL-Cone year

Trial Locations

Locations (3)

Juntendo University School of Medicine

🇯🇵

Bunkyo-ku, Tokyo, Japan

Yamaguchi University Graduate School of Medicine

🇯🇵

Ube, Yamaguchi, Japan

Kyoto University Graduate School of Medicine

🇯🇵

Kyoto, Japan

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