Low-density lipoprotein cholesterol lowering therapies: what is on the horizon?
Elevated low-density lipoprotein cholesterol (LDL-C) levels are associated with an increased risk for cardiovascular disease (CVD). Statins have been the cornerstone of lipid therapy to lower LDL-C for the past two decades, but despite significant clinical efficacy in a majority of patients, a large residual risk remains for the development of initial or recurrent atherosclerotic CVD. In addition, owing to the side-effects, a significant percentage of patients cannot tolerate any statin dose or a high enough statin dose. Thus, novel therapeutic agents are currently being developed to lower LDL-C levels further. This review will highlight these novel therapeutic agents including antisense oligonucleotides focused on apolipoprotein B, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and microsomal triglyceride transfer protein inhibitors. For each therapeutic class, an overview of mechanism of action, pharmacokinetic data, and efficacy/safety evidence will be discussed.
aEinstein Institute for Heart and Vascular Health, Einstein Medical Center bJefferson Medical College, Philadelphia, Pennsylvania, USA.
Ramprasad
R
Gadi
Vincent M
VM
Figueredo
D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D008078:Cholesterol, LDL / Q000097:blood*; D002986:Clinical Trials as Topic; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D020319:Oligodeoxyribonucleotides, Antisense / Q000627:therapeutic use; D009841:Oligonucleotides / Q000627:therapeutic use; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases
D000924:Anticholesteremic Agents; D002352:Carrier Proteins; D008078:Cholesterol, LDL; D020319:Oligodeoxyribonucleotides, Antisense; D009841:Oligonucleotides; C106092:microsomal triglyceride transfer protein; C524142:mipomersen; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases