Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors are novel 
agents indicated for the treatment of hyperlipidemia. Inhibition of PCSK9 
produces an increase in surface low-density lipoprotein (LDL) receptors and 
increases removal of LDL from the circulation. Alirocumab (Praluent; 
Sanofi/Regeneron, Bridgewater, NJ) and evolocumab (Repatha; Amgen, Thousand 
Oaks, CA) are currently available and approved for use in patients with 
heterozygous familial hypercholesterolemia, homozygous familial 
hypercholesterolemia, and clinical atherosclerotic cardiovascular disease. 
Bococizumab (RN316; Pfizer, New York, NY) is currently being studied in similar 
indications, with an estimated approval date in late 2016. The pharmacodynamic 
effects of PCSK9 inhibitors have been extensively studied in various patient 
populations. They have been shown to produce significant reductions in LDL and 
are well tolerated in clinical studies, but they are very costly when compared 
with statins, the current mainstay of hyperlipidemia treatment. Clinical outcome 
studies are underway, but not yet available; however, meta-analyses have pointed 
to a reduction in cardiovascular death and cardiovascular events with the use of 
PCSK9 inhibitors. This review will discuss the novel mechanism of action of 
PCSK9 inhibitors, the results of clinical studies, and the clinical 
considerations of these agents in current therapy.