The Roles of Apo(a) Size, Phenotype, and Dominance Pattern in PCSK9-inhibition Induced Reduction in Lp(a) With Alirocumab

Byambaa Enkhmaa, Erdembileg Anuurad, Wei Zhang, Kun Yue, Ching-Shang Li, Lars Berglund

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Abstract

An elevated level of lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease. 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 apolipoprotein(a) [apo(a)] size polymorphism, phenotype, and dominance pattern and LDL-C-reduction was evaluated in a pooled analysis of 155 hypercholesterolemic patients (75 with heterozygous familial hypercholesterolemia) from 2 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 vs. baseline. Percent reduction in Lp(a) level with alirocumab was similar across apo(a) phenotypes (single vs. double bands) and carriers and non-carriers of a small size apo(a) (≤22 Kringles). Percent reduction in LDL-C correlated significantly with 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 presence or absence of a small size apo(a).

Original languageEnglish (US)
JournalJournal of Lipid Research
DOIs
StateE-pub ahead of print - Aug 10 2017
Externally publishedYes

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