title: Alirocumab for the treatment of hypercholesterolemia.
abstract: Alirocumab is a human monoclonal antibody inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) that is administered by subcutaneous injection every 2 weeks. Area covered: Herein, the authors discuss the background to inhibition of PCSK9 and the pharmacodynamics, pharmacokinetics and clinical trials with alirocumab. Alirocumab produces substantial reductions in low density lipoprotein cholesterol (LDL-C) in patients with and without background statin treatment. The safety profile appears very promising from the relatively short term studies that have been completed but there are some remaining concerns about long term risks of neurocognitive events and developing diabetes. Expert opinion: The profound reduction in LDL-C with alirocumab is most likely to translate into cardiovascular benefits in the ODYSSEY OUTCOMES trial and is unlikely in itself to result in any major adverse effects. The high cost and the current lack of long-term safety and efficacy data will restrict the use of alirocumab to patients who have high cardiovascular risk from established atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia and who are unable to achieve LDL-C targets with maximally tolerated dose of statins with or without other lipid-lowering drugs. When further data become available, these indications are likely to be expanded.
authors.affiliation: a Research Center for Translational Medicine , Shanghai East Hospital Affiliated to Tongji University School of Medicine , Shanghai , China.|b Department of Medicine & Therapeutics , The Chinese University of Hong Kong , Shatin , Hong Kong.
authors.forename: Brian
authors.initials: B
authors.lastname: Tomlinson
authors.affiliation: b Department of Medicine & Therapeutics , The Chinese University of Hong Kong , Shatin , Hong Kong.
authors.forename: Miao
authors.initials: M
authors.lastname: Hu
authors.affiliation: a Research Center for Translational Medicine , Shanghai East Hospital Affiliated to Tongji University School of Medicine , Shanghai , China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: c Division of Cardiology, Department of Internal Medicine, Wan Fang Hospital , Taipei Medical University , Taipei City , Taiwan.
authors.forename: Paul
authors.initials: P
authors.lastname: Chan
authors.affiliation: d Department of Cardiac Surgery, Shanghai East Hospital , Tongji University , Shanghai , China.
authors.forename: Zhong-Min
authors.initials: ZM
authors.lastname: Liu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D002317:Cardiovascular Agents / Q000008:administration & dosage; D008078:Cholesterol, LDL / Q000037:antagonists & inhibitors / Q000097:blood; D002986:Clinical Trials as Topic / Q000379:methods; D004359:Drug Therapy, Combination; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9 / Q000097:blood*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002317:Cardiovascular Agents; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C571059:alirocumab
keywords: Alirocumab; atherosclerotic cardiovascular disease; heterozygous familial hypercholesterolemia; low-density lipoprotein cholesterol; proprotein convertase subtilisin/kexin type 9