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

Hypercholesterolemia Clinical Trial

Official title:

Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00242944
• Other study ID #: H17-49
• Status: Completed
• Phase: Phase 4
• Start date: November 2005
• Est. completion date: March 2008

Study information

• Verified date: October 2023
• Source: Kyoto University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 307
• Est. completion date: March 2008
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Coronary Disease
• Hypercholesterolemia

Intervention

Drug:
• Pitavastatin
Pitavastatin 4mg per day
• Atorvastatin
Atorvastatin 20mg per day

Locations

Country	Name	City	State
Japan	Juntendo University School of Medicine	Bunkyo-ku	Tokyo
Japan	Kyoto University Graduate School of Medicine	Kyoto
Japan	Yamaguchi University Graduate School of Medicine	Ube	Yamaguchi

Sponsors (3)

Lead Sponsor	Collaborator
Kyoto University	Juntendo University, Yamaguchi University Hospital

Country where clinical trial is conducted

Japan, 

References & Publications (2)

Hiro T, Kimura T, Morimoto T, Miyauchi K, Nakagawa Y, Yamagishi M, Ozaki Y, Kimura K, Saito S, Yamaguchi T, Daida H, Matsuzaki M; JAPAN-ACS Investigators. Effect of intensive statin therapy on regression of coronary atherosclerosis in patients with acute — View Citation

Miyauchi K, Kimura T, Morimoto T, Nakagawa Y, Yamagishi M, Ozaki Y, Hiro T, Daida H, Matsuzaki M. Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome (JAPAN-ACS): rationale and design. Circ J. 2006 Dec;70(12):1624-8. doi: 10.1253/circj.70.1624. Erratum In: Circ J. 2007 Jan;71(1):172. — View Citation

Outcome

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