The roles of apo(a) size, phenotype, and dominance pattern in PCSK9-inhibition-induced reduction in Lp(a) with alirocumab.
J Lipid Res
; 58(10): 2008-2016, 2017 10.
Article
em En
| MEDLINE
| ID: mdl-28798072
ABSTRACT
An elevated level of lipoprotein (a) [Lp(a)] is a risk factor for CVD. Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, is reported to reduce Lp(a) levels. The relationship of Lp(a) reduction with apo(a) size polymorphism, phenotype, and dominance pattern and LDL cholesterol (LDL-C) reduction was evaluated in a pooled analysis of 155 hypercholesterolemic patients (75 with heterozygous familial hypercholesterolemia) from two clinical trials. Alirocumab significantly reduced total Lp(a) (pooled median -21%, P = 0.0001) and allele-specific apo(a), an Lp(a) level carried by the smaller (median -18%, P = 0.002) or the larger (median -37%, P = 0.0005) apo(a) isoform, at week 8 versus baseline. The percent reduction in Lp(a) level with alirocumab was similar across apo(a) phenotypes (single vs. double bands) and carriers and noncarriers of a small size apo(a) (≤22 kringles). The percent reduction in LDL-C correlated significantly with the percent reduction in Lp(a) level (r = 0.407, P < 0.0001) and allele-specific apo(a) level associated with the smaller (r = 0.390, P < 0.0001) or larger (r = 0.270, P = 0.0183) apo(a) sizes. In conclusion, alirocumab-induced Lp(a) reduction was independent of apo(a) phenotypes and the presence or absence of a small size apo(a).
Palavras-chave
apolipoprotein (a); apolipoproteins; clinical studies; drug therapy/hypolipidemic drugs; familial hypercholesterolemia; genetic variability; hypercholesterolemic; lipoprotein (a); lipoproteins; low density lipoprotein cholesterol reduction; monoclonal antibody; proprotein convertase subtilisin/kexin type 9
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fenótipo
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Inibidores de Proteases
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Apoproteína(a)
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Inibidores de PCSK9
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Anticorpos Monoclonais
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
J Lipid Res
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Canadá