Advances in the field of proprotein convertase subtilisin kexin type 9 inhibitors

摘要

Purpose of reviewProprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors are promising therapies that inhibit the degradation of low-density lipoprotein (LDL) receptors in the hepatocyte and thus increase LDL cholesterol (LDL-C) uptake from the blood. This review summarizes main findings in the field of PCSK9 inhibitors, from basic mechanism to clinical studies, and aims to provide a contemporary and practical overview of the clinical implication and future directions with PCSK9 inhibitors.Recent findingsMonoclonal antibodies that inhibit PCSK9 reduce LDL-C levels by 40-70% across a wide range of patients with various LDL-C levels, and with different lipid-lowering regimens. These agents significantly reduce apolipoprotein B and lipoprotein (a), may have a potential role in plaque stabilization in acute coronary syndromes, and are safe and tolerable, even among statin-intolerant patients. Preliminary data with evolocumab and alirocumab demonstrate the potential reduction of cardiovascular (CV) events. These PCSK9 inhibitors were recently approved for clinical use, and recommended in the 2016 American College of Cardiology expert consensus document for nonstatin therapy for LDL-C lowering.SummaryPCSK9 inhibitors are novel promising therapies to reduce LDL-C. Ongoing phase 3 clinical trials with more than 70000 high-risk patients will examine their safety and efficacy in reducing cardiovascular disease.