457-P: One-Year Administration of Anti-PCSK9 Antibody Is Enough to Stabilize Vulnerable Coronary Plaques in Diabetic Patients, which Are Resistant to Intensive Statin Therapy

Purpose: Coronary plaque progression despite very low levels of LDL-C has been reported in the patients with coronary artery disease (CAD) who received intensive statin therapy (IST). Coronary CT Angiography (CCTA) has been applied to evaluate vulnerable coronary plaques having low attenuation of CT value. The major function of PCSK9 is the binding to hepatic LDL receptors, leading to their degradation. PCSK9 is produced also in vascular smooth muscle cells constituting the atherosclerotic lesion in addition to hepatocytes. PCSK9 promotes foam cell formation by suppressing the excretion of cholesterol from macrophages. Statin is demonstrated to promote PCSK9 production. PCSK9 has been proposed to play a crucial role in the pathogenesis of IST resistance. The present study was performed to establish a novel therapeutic approach to IST resistant vulnerable plaque of coronary artery in diabetic patients. Methods: The present study included 142 T2DM patients with non-FHC asymptomatic CAD who developed vulnerable coronary plaques despite IST over 2 years. CCTA by use of 320-slice CT was applied to evaluate vulnerable coronary plaques. During the administration of anti-PCSK9 antibody, changes in serum lipids and CT value of vulnerable coronary plaques were determined. Results: During 1 year administration of anti-PCSK9 antibody, 74% decrease in serum LDL-C was observed. Also, improvement of vulnerable coronary plaque, e.g., rise in the CT value of plaque (from 43.2 ±12.0 HU to 128.5 ± 52.3 HU, p