Rationale and design of randomized evaluation of aggressive or moderate lipid lowering therapy with pitavastatin in coronary artery disease (REAL-CAD) trial

Large-scale clinical trials in patients in Western countries with coronary artery disease (CAD) have found that aggressive lipid-lowering therapy using high-dose statins reduces cardiovascular (CV) events further than low-dose statins. However such evidence has not yet been fully established in Asian populations including in Japan. The Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study addresses whether intensification of statin therapy improves clinical outcomes in Japanese patients with CAD. REAL-CAD is a prospective multicenter randomized open-label blinded-endpoint physician-initiated phase 4 trial in Japan. The study will recruit up to 12,600 patients with stable CAD. Patients are assigned to receive either pitavastatin 1 mg/day or pitavastatin 4 mg/day. LDL-C levels are expected to reach approximate mean values of 100 mg/dL in the low-dose pitavastatin group 80 mg/dL in the high-dose group. The primary endpoint is the time to occurrence of a major CV event including CV death non-fatal myocardial infarction non-fatal ischemic strokeunstable angina requiring emergency hospitalization during an average of 5 years. The large number of patients the long follow-up period in the REAL-CAD study should ensure that there is adequate power to definitively determine if reducing LDL-C levels to approximately 80 mg/dL by high-dose statin can provide additional clinical benefit. After the study is completed we will have categorical evidence on the optimal statin dose target LDL-C level for secondary prevention in Japanese patients.