Abstract 10846: Long-term Effects of Ezetimibe Plus Statin Combination vs Double-dose Statin Therapy on Low-density Lipoprotein Cholesterol Lowering in Coronary Artery Disease Patients Pre-treated with Statins; Focus on Proprotein Convertase Subtilisin/Kexin Type 9

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to hepatic LDL receptor, causing its subsequent degradation. Although statin therapy is known to increase concentrations of PCSK9, the relationship between long-term treatment with ezetimibe + statin and PCSK9 is not fully elucidated. Methods: We performed a multi-center, prospective, randomized trial involving 150 patients with coronary artery disease (CAD) whose LDL-C level ≥70 mg/dL after treatment with atorvastatin 10mg/day or rosuvastatin 2.5mg/day. The patients were assigned to receive ezetimibe 10mg/day plus statin (n=78) or double-dose statin (n=75) for 52 weeks. We measured serum LDL-C levels and plasma PCSK9 concentrations by ELISA at baseline, 12 weeks and 52 weeks. Results: Baseline patient’s characteristics did not differ in both 2 groups. Although the greater LDL-C reduction was observed from baseline to 12 weeks in the ezetimibe + statin group compared to the double-dose statin group (-28.7±19.7 mg/dL vs. -16.5±17.0 mg/dL, P Conclusions: Although rapid increase in PCSK9 levels was observed in the double-dose statin group, PCSK9 levels unchanged in the ezetimibe + statin group in the first 12 weeks. Moreover, the ezetimibe + statin group provided a greater and stable LDL-C reduction compared to double-dose statin group despite the fact that late increase in PCSK9 levels was observed after 12 weeks. These findings may explain the advantage of combination therapy in LDL-C lowering in CAD patients pretreated with statin.