title: Focus on PCSK9 Inhibitors: From Genetics to Clinical Practice.
abstract: Elevation of low-density lipoprotein cholesterol (LDL-C) is an important cause of atherosclerotic cardiovascular disease (ASCVD). Over the years, clinical outcome studies with LDL-C lowering agents have revealed that reducing LCL-C levels is effective in reducing rates of major ASCVD events. Although secondary factors play a role in clinical expression, severe lipid disorders often have a strong genetic component. Genetic revelations have provided novel targets for improving LDL-C management in high-risk individuals. Most recently, researchers have explored how the inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) alters LDL metabolism and lowers LDL-C levels to achieve lipid goals and potentially reduce ASCVD risk in patients with severe lipid disorders, including familial hypercholesterolemia (FH). This CMHC Spotlight article summarizes the clinical evidence demonstrating the safety, tolerability, and efficacy of PCSK9 inhibitors in lowering LDL-C levels. Reductions in LDL-C levels by PCSK9 inhibitors alone in patients who are statin intolerant or combined with maximally tolerated statins in patients with severe lipid disorders demonstrate the potential for reduced morbidity and mortality associated with ASCVD.
authors.affiliation: a Thrombolysis in Myocardial Infarction (TIMI) Study Group, Division of Cardiovascular Medicine , Brigham and Women's Hospital.|b Department of Medicine , Harvard Medical School , Boston , MA.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
authors.affiliation: c NYU Medical School, NYU Center for CVD Prevention , Bellevue Hospital Lipid Clinic , New York , NY.
authors.forename: James A
authors.initials: JA
authors.lastname: Underberg
authors.affiliation: d Jacksonville Center for Clinical Research.|e Academy of Physicians in Clinical Research , Jacksonville , FL.
authors.forename: Michael
authors.initials: M
authors.lastname: Koren
authors.affiliation: f MB Clinical Research.|g American Society for Preventive Cardiology.|h The FH Foundation.
authors.forename: Seth J
authors.initials: SJ
authors.lastname: Baum
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D008078:Cholesterol, LDL / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D019468:Disease Management; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D007155:Immunologic Factors / Q000494:pharmacology; D052439:Lipid Metabolism Disorders / Q000150:complications / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9 / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D008078:Cholesterol, LDL; D007155:Immunologic Factors; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: LDL-C; PCSK9 inhibitors; familial hypercholesterolemia; lipid disorders; statin intolerance