title: Novel therapeutic agents for lowering low density lipoprotein cholesterol.
abstract: Elevated low density lipoprotein cholesterol (LDL-C) levels have been associated with an increased risk for cardiovascular disease (CVD). Despite a 25-30% reduction in CVD risk with LDL-C reducing strategies, there is still a significant residual risk. Moreover, achieving target LDL-C values in individuals at high CVD risk is sometimes limited because of tolerability and/or efficacy. Thus, novel therapeutic agents are currently being developed to lower LDL-C levels further. This review will highlight some of these therapeutic agents including anti-sense oligonucleotides focused on apolipoprotein B, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, microsomal triglyceride transfer protein inhibitors, and thyromimetics. For each therapeutic class, an overview of the mechanism of action, pharmacokinetic data, and efficacy/safety evidence will be provided.
authors.affiliation: Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada, N6A 5K8. tisjoy@hotmail.com
authors.forename: Tisha R
authors.initials: TR
authors.lastname: Joy
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D040761:Biomimetic Materials / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood*; D015536:Down-Regulation; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012697:Serine Endopeptidases / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D015415:Biomarkers; D002352:Carrier Proteins; D008078:Cholesterol, LDL; D016376:Oligonucleotides, Antisense; D047428:Protein Kinase Inhibitors; D013963:Thyroid Hormones; C106092:microsomal triglyceride transfer protein; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases