Yokohama Assessment of Fluvastatin, Pravastatin, Pitavastatin and Atorvastatin in Acute Coronary Syndrome (Yokohama-ACS) (Yokohama-ACS)

The purpose of this study is to compare the effects of fluvastatin, pravastatin, pitavastatin, and atorvastatin on coronary plaque volume in patients with acute coronary syndrome, and to clarify the impact of moderate and intensive lipid lowering therapy on coronary plaque volume, serum lipids, and inflammation markers in patients with acute coronary syndrome in Japanese.

Study Overview

• Status: Completed
• Conditions: Coronary Disease; Hypercholesterolemia
• Intervention / Treatment: Drug: Atorvastatin; Drug: Pravastatin; Drug: Pitavastatin; Drug: Fluvastatin

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 whether we need to lower LDL-C level less than the 70mg/dL or not in Japanese population.

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), whereas therapy with pravastatin (40 mg/day) showed a slight increase (2.7%) in plaque volume over 18 months in Western population.

In Japanese population, MEGA study have shown the effect of moderate lipid lowering therapy in primary prevention of cardiovascular events. However, the effect of moderate lipid lowering therapy in secondary prevention of cardiovascular events is unknown.

Pravastatin and fluvastatin are the statin which has been administered in Japan for several years.

Although LDL-C lowering effect of these statins were less strong than new generation statins, their safeｔｙ profile have been well established. Fluvastatin were expected to reduce coronary plaque because of its high affinity to arterial tissue and antioxygenic effect compared with pitavastatin, but the effect on human coronary plaque has not been reported.

Relative plaque regression rate between intensive and moderate lipid lowering therapy would clarify the ideal level of target LDL-C in Japanese population. Furthermore, the different effect on coronary plaque between pravastatin and fluvastatin which have similar LDL-C lowering effect and different affinity to arterial tissue would determine the superior lipid lowering regimen to affect coronary plaque volume.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Yokohama, Japan
    • Yokohama City University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients who have been diagnosed as acute coronary syndrome, and successful percutaneous coronary intervention (PCI) were performed with intravascular ultrasound (IVUS) guidance.
2. Patients having coronary plaques (≧ 500 µm in thickness or % plaque of 20% or more at ≧ 5 mm distal or proximal to the previously treated area in the same branch of coronary artery.

3. Patients with hypercholesterolemia as defined by any of the following criteria:

   • TC ≧ 220 mg/dL
   • LDL-C ≧ 140 mg/dL Cholesterol-lowering treatment is allowed according to the investigator's judgement when LDL-C ≧ 100 mg/dL or TC ≧ 180 mg/dL.
4. Patients with written consent by their own volition after being provided sufficient explanation for their participation in this clinical trial.
5. Patients 20 years or older at the time of their consent.

Exclusion Criteria:

1. Patients with bypass graft or in-stent restenosis at the site of PCI.
2. Patients who received PCI in the past on the lesion where the evaluation of coronary plaque volume is planned.
3. Patients who had plaques in a non-culprit site and might receive PCI during the treatment period.
4. Patients receiving lipid-lowering drugs (statins, fibrates, probucol, nicotinic acid or cholesterol absorption inhibitors).
5. Patients with familial hypercholesterolemia.
6. Patients with cardiogenic shock.
7. Patients receiving cyclosporine.
8. Patients with any allergy to pravastatin, fluvastatin, pitavastatin, or atorvastatin.
9. Patients with hepatobiliary disorders.
10. Pregnant women, women suspected of being pregnant, or lactating women.
11. Patients with renal disorders or undergoing dialysis.
12. Patients who are ineligible in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 2	Drug: Pravastatin
Active Comparator: 1	Drug: Fluvastatin
Active Comparator: 3	Drug: Pitavastatin
Active Comparator: 4	Drug: Atorvastatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the percent change in coronary plaque volume the percent change in integrated backscatter signal obtained by integrated backscatter IVUS	9-11 month

Secondary Outcome Measures

Outcome Measure	Time Frame
absolute change from baseline in coronary plaque volume	9-11 month
absolute and percent changes in minimal lumen diameter(MLD) and percent(%) stenosis	9-11 month
absolute and percent changes in total cholesterol(TC);low-density lipoprotein(LDL)-cholesterol(LDL-C)	9-11 month

Collaborators and Investigators

• Sponsor: Yokohama City University Medical Center
• Investigators: Principal Investigator: Naohiro Komura, Yokohama City University Medical Center

Publications and helpful links

General Publications

• Matsushita K, Hibi K, Komura N, Kimura Y, Matsuzawa Y, Konishi M, Maejima N, Iwahashi N, Kosuge M, Ebina T, Tamura K, Kimura K. Impact of serum lipoprotein (a) level on coronary plaque progression and cardiovascular events in statin-treated patients with acute coronary syndrome: a yokohama-acs substudy. J Cardiol. 2020 Jul;76(1):66-72. doi: 10.1016/j.jjcc.2020.01.005. Epub 2020 Feb 7.
• Hibi K, Sonoda S, Kawasaki M, Otsuji Y, Murohara T, Ishii H, Sato K, Koshida R, Ozaki Y, Sata M, Morino Y, Miyamoto T, Amano T, Morita S, Kozuma K, Kimura K, Fujiwara H; Ezetimibe-ACS Investigators. Effects of Ezetimibe-Statin Combination Therapy on Coronary Atherosclerosis in Acute Coronary Syndrome. Circ J. 2018 Feb 23;82(3):757-766. doi: 10.1253/circj.CJ-17-0598. Epub 2017 Dec 7.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: October 25, 2007
• First Submitted That Met QC Criteria: October 25, 2007
• First Posted (Estimate): October 26, 2007

Study Record Updates

• Last Update Posted (Estimate): February 17, 2010
• Last Update Submitted That Met QC Criteria: February 16, 2010
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Coronary Disease; Hypercholesterolemia; Acute Coronary Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Pravastatin; Pitavastatin
• Other Study ID Numbers: Yokohama-ACS