Response to PCSK9 Inhibition Based on LDL Receptor Function in Familial Hypercholesterolemia

In individuals with heterozygous familial hypercholesterolemia (HeFH), is low-density lipoprotein cholesterol (LDL-C) reduction with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy associated with residual low-density lipoprotein receptor (LDLR) function?In this nonrandomized clinical trial of 703 genotyped participants with treated with the PCSK9 inhibitor lerodalcibep, assessment of response according to LDLR pathogenic variant classification showed that reductions in LDL-C were independent of LDLR variant functional activity.These findings suggest that in individuals with HeFH, LDL-C reductions with PCSK9 inhibition were likely mediated predominantly by upregulation of the unaffected wild-type LDLR.

Corresponding Author: Frederick J. Raal, DSC, Carbohydrate and Lipid Metabolism Research Unit, Department of Medicine, Witwatersrand University, 7 York Rd, Parktown, 2193 Johannesburg, South Africa (frederick.raal@wits.ac.za).

Link to the article in your story

We encourage you to link out to this article in your story using the link below. It includes an access token that will give free access to the article for your readers up to one year after publication. (The link will be live after the article publishes and embargo is lifted.)

Please see the article for additional information, including full author list, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Need more information? Contact us.