Clinical trial NCT01042730: Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease (REAL-CAD)
Official title: Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease (REAL-CAD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Artery Disease
Keywords: Pitavastatin
Coronary Artery Disease
Cardiovascular Disease
Lead sponsor: Juntendo University
Sponsor class: OTHER
Collaborators: name: Tokyo University
name: Yamaguchi University Hospital
name: Tohoku University
name: Kyoto University
name: Kumamoto University
First posted: 2010-01-06
Enrollment: 13054
Sex: ALL
Minimum age (years): 20
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Occurrence of one of following events(Cardiovascular death, Non-fatal Myocardial Infarction (MI), Non-fatal Cerebral Infarction (CI), Unstable angina requiring urgent hospitalization)
timeFrame: 3-6 years
Secondary outcomes:
measure: Composite cardiovascular events
timeFrame: 3-6 years
measure: Composite coronary heart disease events
timeFrame: 3-6 years
measure: Composite cerebrovascular events
timeFrame: 3-6 years
measure: Death events
timeFrame: 3-6 years
measure: Heart disease events
timeFrame: 3-6 years
measure: Cerebrovascular events
timeFrame: 3-6 years
measure: The other events
timeFrame: 3-6 years
Other outcomes:
Locations:
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Tokyo
country: Japan
facility: Juntendo University School of Medicine
Study officials:
affiliation: Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine
name: Ryozo Nagai, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine
name: Masunori Matsuzaki, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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. doi: 10.1161/CIR.0000000000000676.