title: Evolocumab in the treatment of dyslipidemia: pre-clinical and clinical pharmacology.
abstract: BACKGROUND
  Statins are the mainstay of lipid-lowering therapies targeted at reducing cardiovascular risk. However, they do not completely obviate risk, not all patients tolerate them, and they are not sufficiently effective in patients with very high plasma levels of low-density lipoprotein-cholesterol (LDL-C) such as those with familial hypercholesterolemia (FH) or patients with elevated plasma levels of lipoprotein(a) [Lp(a)]. Recent advances in the understanding of lipoprotein metabolism have led to the development of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors including evolocumab , which lowers plasma levels of LDL-C by 50 - 75% as monotherapy or in combination with statin therapy.
  
  
  METHODS
  We discuss in this review the rationale and background behind the development of evolocumab, and its pharmacodynamics and pharmacokinetics. We then discuss the current state-of-play of relevant clinical trials.
  
  
  CONCLUSIONS
  The dramatic reduction in plasma levels of LDL-C attributable to evolocumab is anticipated to translate into lower rates of atherosclerotic cardiovascular disease, but this hypothesis remains to be proven. Also to be established are the long-term safety and economic benefits of evolocumab. PCSK9 inhibitors will also probably provide a valuable option for patients with statin intolerance, those with FH and patients with elevated plasma levels of Lp(a).
authors: a 1 Royal Perth Hospital, Lipid Disorders Clinic, Cardiovascular Medicine , Perth, Australia.
authors: Michael M
authors: MM
authors: Page
authors: Gerald F
authors: GF
authors: Watts
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D008078:Cholesterol, LDL / Q000097:blood; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C577155:evolocumab
keywords: alirocumab; bococizumab; evolocumab; familial hypercholesterolemia; low density lipoprotein cholesterol; proprotein convertase subtilisin/kexin type 9 inhibitors; statins