title: Safety and tolerability of injectable lipid-lowering drugs: a review of available clinical data.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: S. Orsola-Malpighi University Hospital, Medical and Surgical Sciences Department, Internal Medicine Unit , Pad. 2 - Via Albertoni 15 - 40138 Bologna , Italy +39 3498558017 ; +39 516826125 ; arrigo.cicero@unibo.it.
authors: Arrigo F G
authors: AF
authors: Cicero
authors: Elisa
authors: E
authors: Tartagni
authors: Sibel
authors: S
authors: Ertek
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D007267:Injections; D009841:Oligonucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; 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; D009841:Oligonucleotides; C524142:mipomersen; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C577155:evolocumab; C571059:alirocumab
keywords: hypercholesterolemia; lipid-lowering drugs; mipomersen; proprotein convertase subtilisin/kexin type 9