Atherosclerosis stabilization with PCSK-9 inhibition: An evolving concept for cardiovascular prevention.

Abstract

Monoclonal antibodies (mAbs) to proprotein convertase subtilisin/kexin type 9 (PCSK-9) can further lower LDL-C by ≥60% in statin-treated patients. Preliminary data suggest they may reduce cardiovascular (CVD) events. Ongoing PCSK-9 mAb cardiovascular outcomes trials could provide the opportunity to determine whether a "legacy effect" similar to that observed for statins will occur over the post-trial observation period. We hypothesize these trials could demonstrate that (1) very aggressive LDL-C lowering with PCSK-9 mAbs added to background statin therapy will induce extensive atherosclerosis stabilization and regression in the large majority of treated patients, and (2) continued maintenance therapy with high intensity statin therapy (with or without ezetimibe) should then inhibit new plaque formation, with a long-term prevention of CVD events. The necessity of expensive lifetime treatment with PCSK-9 inhibitors could then be avoided in all but a small subset of patients who could benefit from longer treatment.

• Authors: Jennifer G Robinson, Donald D Heistad, Keith A A Fox
• Journal: Atherosclerosis (Atherosclerosis) Vol. 243 Issue 2 Pg. 593-7 (Dec 2015) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 26545013 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Biomarkers
• Cholesterol, LDL
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Hypolipidemic Agents
• Serine Proteinase Inhibitors
• PCSK9 protein, human
• Proprotein Convertase 9
• Proprotein Convertases
• Serine Endopeptidases

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Atherosclerosis (blood, drug therapy, enzymology, etiology)
• Biomarkers (blood)
• Cholesterol, LDL (blood)
• Drug Therapy, Combination
• Dyslipidemias (blood, complications, drug therapy, enzymology)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Hypolipidemic Agents (therapeutic use)
• Molecular Targeted Therapy
• Plaque, Atherosclerotic
• Proprotein Convertase 9
• Proprotein Convertases (antagonists & inhibitors, immunology, metabolism)
• Secondary Prevention (methods)
• Serine Endopeptidases (immunology, metabolism)
• Serine Proteinase Inhibitors (therapeutic use)
• Treatment Outcome