INTRODUCTION: Reduction of plasma low-density lipoprotein (LDL) cholesterol 
concentration with statins reduces adverse cardiovascular outcomes. However, 
lack of efficacy and intolerance of statins in many patients requires 
alternative treatments. Currently available non-statin alternatives include bile 
acid sequestrants, the cholesterol absorption inhibitor ezetimibe, niacin-based 
preparations and fibrates; however, each of these has limitations. Newer agents 
for LDL cholesterol reduction include the cholesterol ester transfer protein 
inhibitors, the microsomal triglyceride transfer protein inhibitor lomitapide, 
the apolipoprotein B antisense oligonucleotide mipomersen and several molecules 
that inhibit or interfere with proprotein convertase subtilisin/kexin 9 (PCSK9).
AREAS COVERED: Among the various PCSK9 inhibitors, human data are available for 
monoclonal antibodies against PCSK9 of which the two most advanced are 
alirocumab (SAR236553/REGN727) and AMG 145. Phase II studies of these agents as 
monotherapy or in combination with statins have shown reductions of LDL 
cholesterol by > 70%, with acceptable safety and tolerability so far.
EXPERT OPINION: Despite their biochemical efficacy, clinical efficacy, reflected 
by reduction of cardiovascular end points, remains to be shown for two leading 
monoclonal antibodies against PSCK9. Other issues to be evaluated with these 
agents over the longer term include development of rare adverse effects and 
potential attenuation of efficacy.