Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease (REAL-CAD)

The purpose of this study is to evaluate the prevention of cardiovascular disease by moderate cholesterol lowering therapy, pitavastatin 1mg/day or aggressive cholesterol lowering therapy, pitavastatin 4mg/day in patients with stable coronary artery disease.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Pitavastatin 1 mg daily or 4 mg daily

Detailed Description

It was already demonstrated by previous clinical trials that statins lower the incidence of death and cardiovascular events in patients with coronary artery disease. However, whether aggressive cholesterol lowering therapy, using high dosage of statins, is more effective than moderate cholesterol lowering therapy for the prevention of cardiovascular events in patients with coronary artery disease has not been studied in Japan.

• Study Type: Interventional
• Enrollment (Actual): 13054
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Japan
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Tokyo, Japan
    • Juntendo University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who met following all criteria are entered in run-in period, loading pitavastatin 1 mg/day for more than 1 month when informed consent was given. (Primary registration)

• Coronary artery disease patients meeting one of the following events

  • History of Acute Coronary Syndrome (AMI or Unstable angina)
  • History of revascularization (PCI or CABG)
  • Diagnosis of ischemic heart disease and coronary artery stenosis as having 75% or higher stenosis according to the AHA classification

• Hypercholesterolemia patients meeting one of following criteria

  • LDL-C is 140 mg/dL or over
  • LDL-C is 100 mg/dL or over and requiring cholesterol lowering drugs judged by attending physicians
  • Patents receiving cholesterol lowering drugs
• Age (≧20 <80 year-old)
• Patients given written informed consent.

Exclusion Criteria:

Exclusion Criteria(Pre-Run-in period)

• Patients planning revascularization
• Malignant tumor in active phase

• Patients who meet contraindication of LIVALO tablet below

  • Patients who have hypersensitivity to LIVALO tablet
  • Patients who have severe liver dysfunction or biliary atresia
  • Patients who are being treated with cyclosporine
  • Pregnant women, women suspected of being pregnant, or lactating women
• Patients who have heart failure NYHA III or greater
• Patients undergoing dialysis
• Patients with familial hypercholesterolemia
• Patients registered in the other clinical trials
• Patients taking prohibited drugs
• Patients who are ineligible in the opinion of the investigator

Exclusion Criteria(Post-Run-in period)

• LDL-C is 120mg/dL or over after Run-in period
• Patients with occurrence of acute coronary syndrome (AMI or Unstable angina) within 3 months
• Patients who have been undergone PCI or CABG within 3 months
• Compliance is less than 50% in Run-in period
• Patients who met primary endpoint in Run-in period.
• Patients who met adverse events in Run-in period and judged as ineligible in the opinion of the investigator
• Patients who are ineligible in the opinion of the investigator

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pitavastatin 1 mg daily	Drug: Pitavastatin 1 mg daily or 4 mg daily; Patients who met all inclusion criteria and did not meet exclusion criteria (1) are entered in run-in period, loading pitavastatin 1 mg/day for more than 1 month when informed consent was given. (Primary registration) After 1 month, patients who did not meet exclusion criteria(2) are randomized to take pitavastatin 1 mg/day or 4 mg/day.; Other Names: LIVALO Tablet
Active Comparator: Pitavastatin 4 mg daily	Drug: Pitavastatin 1 mg daily or 4 mg daily; Patients who met all inclusion criteria and did not meet exclusion criteria (1) are entered in run-in period, loading pitavastatin 1 mg/day for more than 1 month when informed consent was given. (Primary registration) After 1 month, patients who did not meet exclusion criteria(2) are randomized to take pitavastatin 1 mg/day or 4 mg/day.; Other Names: LIVALO Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Occurrence of one of following events(Cardiovascular death, Non-fatal Myocardial Infarction (MI), Non-fatal Cerebral Infarction (CI), Unstable angina requiring urgent hospitalization)	3-6 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Composite cardiovascular events	3-6 years
Composite coronary heart disease events	3-6 years
Composite cerebrovascular events	3-6 years
Death events	3-6 years
Heart disease events	3-6 years
Cerebrovascular events	3-6 years
The other events	3-6 years

Collaborators and Investigators

• Sponsor: Juntendo University
• Collaborators: Kumamoto University; Tokyo University; Kyoto University; Tohoku University; Yamaguchi University Hospital
• Investigators: Principal Investigator: Ryozo Nagai, MD, PhD, Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine; Principal Investigator: Masunori Matsuzaki, MD, PhD, Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine

Publications and helpful links

General Publications

• Sakuma M, Iimuro S, Shinozaki T, Kimura T, Nakagawa Y, Ozaki Y, Iwata H, Miyauchi K, Daida H, Suwa S, Sakuma I, Nishihata Y, Saito Y, Ogawa H, Matsuzaki M, Ohashi Y, Taguchi I, Toyoda S, Inoue T, Nagai R. Optimal target of LDL cholesterol level for statin treatment: challenges to monotonic relationship with cardiovascular events. BMC Med. 2022 Nov 14;20(1):441. doi: 10.1186/s12916-022-02633-5.
• Taguchi I, Iimuro S, Iwata H, Takashima H, Abe M, Amiya E, Ogawa T, Ozaki Y, Sakuma I, Nakagawa Y, Hibi K, Hiro T, Fukumoto Y, Hokimoto S, Miyauchi K, Yamazaki T, Ito H, Otsuji Y, Kimura K, Takahashi J, Hirayama A, Yokoi H, Kitagawa K, Urabe T, Okada Y, Terayama Y, Toyoda K, Nagao T, Matsumoto M, Ohashi Y, Kaneko T, Fujita R, Ohtsu H, Ogawa H, Daida H, Shimokawa H, Saito Y, Kimura T, Inoue T, Matsuzaki M, Nagai R. High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD): A Randomized Superiority Trial. Circulation. 2018 May 8;137(19):1997-2009. doi: 10.1161/CIRCULATIONAHA.117.032615. Erratum In: Circulation. 2019 Apr 2;139(14):e836.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2010
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: January 5, 2010
• First Submitted That Met QC Criteria: January 5, 2010
• First Posted (Estimate): January 6, 2010

Study Record Updates

• Last Update Posted (Actual): May 17, 2021
• Last Update Submitted That Met QC Criteria: May 14, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Cardiovascular Disease; Pitavastatin
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pitavastatin
• Other Study ID Numbers: CSP-LD-09