Emerging innovative therapeutic approaches targeting PCSK9 to lower lipids.
Statins are established therapies for cardiovascular disease prevention and ezetimibe has recently been shown to modestly reduce cardiovascular events when added to background statin therapy. Yet here remains a clear unmet need for additional therapies aimed at lowering low density lipoprotein cholesterol (LDL-C) to further reduce cardiovascular risk. Multiple strategies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition have emerged as effective modalities for LDL-C lowering. PCSK9 monoclonal antibodies are the farthest along in clinical development and alirocumab and evolocumab were approved for clinical use by regulatory agencies in 2015. In addition to robust LDL-C lowering (nearly 50-65% from baseline), they improve other lipid parameters as well. Adverse events associated with these medications are minimal. Importantly, they improve clinical cardiovascular disease outcomes, although long-term study results are awaited. Cost may be an important limiting factor in their use and we propose two possible solutions which can potentially curtail cost.
Departments of Epidemiology & Medicine, Prevention Intervention Center, Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA.
G P S
GP
Shantha
Departments of Epidemiology & Medicine, Prevention Intervention Center, Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA.
J G
JG
Robinson
D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000191:economics / Q000494:pharmacology* / Q000627:therapeutic use*; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000960:Hypolipidemic Agents; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C577155:evolocumab; C571059:alirocumab