PURPOSE OF REVIEW: Proprotein 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 FINDINGS: Monoclonal 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.
SUMMARY: PCSK9 inhibitors are novel promising therapies to reduce LDL-C. Ongoing 
phase 3 clinical trials with more than 70 000 high-risk patients will examine 
their safety and efficacy in reducing cardiovascular disease.