title: Therapeutic Potential and Critical Analysis of the PCSK9 Monoclonal Antibodies Evolocumab and Alirocumab.
abstract: OBJECTIVE
  To review the mechanism of action for PCSK9 monoclonal antibodies and critically evaluate the therapeutic potential of evolocumab and alirocumab in the treatment of hypercholesterolemia.
  
  
  METHODS
  Ovid MEDLINE search from 1980 to August 2015 using the terms PCSK9, evolocumab, and alirocumab with forward and backward citation tracking.
  
  
  METHODS
  English-language trials and studies assessing the mechanism, efficacy, or safety of PCSK9 monoclonal antibodies were included.
  
  
  RESULTS
  PCSK9 monoclonal antibodies have a potent ability to reduce low-density lipoprotein (LDL) by almost 50% in controlled trials: -47.49% (95% CI = -69.6% to -25.4%). They have an acceptable safety profile with no significant elevations in Creatine Kinase (CK) (odds ratio [OR] = 0.72; 95% CI = 0.54 to 0.96) or serious adverse events (OR = 1.01; 95% CI = 0.87 to 1.18), and preliminary evidence suggests reductions in myocardial infarction (OR = 0.49; 95% CI = 0.26 to 0.93). Although it is effective in several familial hypercholesterolemia (FH) patient types, it does not work in homozygous patients with dual allele LDL receptor negative polymorphisms or those who are homozygous for autosomal recessive hypercholesterolemia.
  
  
  CONCLUSIONS
  Although not preferred over statins because of limited clinical trial evidence of cardiovascular event reductions, dosing convenience, and expense, PCSK9 monoclonal antibodies will have a prominent role to play in the treatment of hypercholesterolemia, especially in patients needing large LDL reductions, including patients with many types of FH.
authors.affiliation: University of Connecticut School of Pharmacy and UCONN and Hartford Hospital, Storrs, CT, USA charles.white@uconn.edu.
authors.forename: C Michael
authors.initials: CM
authors.lastname: White
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000235:genetics; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy / Q000235:genetics; D009203:Myocardial Infarction / Q000517:prevention & control; D017410:Practice Guidelines as Topic; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000276:immunology*; D011973:Receptors, LDL / Q000235:genetics; D012697:Serine Endopeptidases / Q000276:immunology*; D016896:Treatment Outcome; D006952:Hyperlipoproteinemia Type III
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C577155:evolocumab; C571059:alirocumab
keywords: PCSK9 inhibitors; alirocumab; evolocumab; familial hypercholesterolemia; hypercholesterolemia