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

Abstract

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<0.0001) was observed. Of the 142 patients, 95 patients finished the administration of the drug. Conclusion: One year administration of anti-PCSK9 antibody produced a significant stabilization of vulnerable coronary plaques in the patients with asymptomatic CAD who are resistant to IST. An analysis of the plaque quality by CCTA is useful method for the evaluation of the effect of the drug on vulnerable coronary plaques. Disclosure A. Hirai: None. K. Fujimura: None. K. Hirai: None. S. Kondo: None. A. Shirakami: None. T. Sakai: None. K. Murata: None. H. Taniai: None. K. Okuzaki: None. T. Kageyama: None.

Changes in Atherosclerotic Plaque Composition with Anti-Lipid Therapy as Detected by Coronary Computed Tomography Angiography

“…This infers stabilization of vulnerable plaque in the setting of diabetic patients on intensive statin therapy with vulnerable plaque seen on CCTA. The conclusion was drawn that a one-year administration of PCSK9 inhibitor therapy produced significant stabilization of vulnerable plaque in patients with asymptomatic coronary artery disease who are resistant to intensive statin therapy [21].…”