INTRODUCTION: To answer the need of a better low-density lipoprotein (LDL) 
cholesterol control in statin-treated patients at high risk for cardiovascular 
disease, new injectable lipid-lowering drugs with innovative mechanisms of 
action are in advanced phase of development or have just been approved.
AREAS COVERED: Evolocumab and alirocumab are fully human monoclonal antibodies 
inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) that binds 
to hepatic LDL receptor and prevents it from normal recycling by targeting it 
for degradation. Mipomersen specifically binds to a segment of the human 
apolipoprotein B100 messenger RNA, blocking the translation of the gene product. 
Phase II (for evolocumab and alirocumab) and III (for evolocumab) trials show 
that PCSK9 inhibitors are equally well tolerated, with adverse events mainly 
limited to mild-to-moderate nasopharyngitis, injection-site pain, arthralgia and 
back pain. Mipomersen use is mainly associated to hepatosteatosis, increased 
transaminases (> 3 times the upper limit of normal), mild-to-moderate 
injection-site reactions and flu-like symptoms.
EXPERT OPINION: PCSK9 inhibitors have demonstrated their good safety and 
tolerability in a large number of subjects with different clinical conditions, 
including statin-intolerance, enlarging their potential use in a broader range 
of patients. Further data on long-term mipomersen safety are required.