Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

HoFH Patients’ Varied Response to PCSK9 Inhibition

Arterioscler Thromb Vasc Biol; ePub 2017 Dec 28; Thedrez, et al

Residual low-density lipoprotein receptor (LDLR) expression is a major determinant of low-density lipoprotein cholesterol (LDL-C) levels and may drive their individual response to evolocumab, a recent study found. Lymphocytes were isolated from 22 HoFH patients in the TAUSSIG trial. 10 patients were true homozygotes (FH1/FH1) and 5 identical compound heterozygotes (FH1/FH2). Lymphocytes were plated with our without mevastatin, recombinant PCSK9 (rPCSK9), or a PCSK9-neutralizing antibody. Researchers found:

  • All HoFH lymphocytes had reduced cell surface LDLR expression compared with non-FH lymphocytes, for each treatment modality.
  • Lymphocytes from FH1/FH2 patients displayed the lowest LDLR expression levels followed by lymphocytes from FH1/FH2 patients.
  • Mevastatin increased, whereas rPCSK9 reduced LDLR expression.
  • Significant positive correlations were found between levels of LDLR expression and the percentage reduction in LDL-C on evolocumab treatment.


Thedrez A, Blom DJ, Ramin-Mangata S, et al. Homozygous familial hypercholesterolemia patients with identical mutations variably express the LDLR (low-density lipoprotein receptor). Implications for the efficacy of evolocumab. [Published online ahead of print December 28, 2017]. Arterioscler Thromb Vasc Biol. doi:10.1161/ATVBAHA.117.310217.

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Racial Differences in Statin Use, JAMA Cardiol; ePub 2018 Jun 13; Nanna, et al

LLT Use in Patients with Elevated LDL-C, Circ Cardiovasc Qual Outcomes; ePub 2018 May 10; Virani, et al

Evolocumab in Differing Patient Populations , J Pharmacokinet Pharmacodyn; ePub 2018 May 7; Kuchimanchi, et al

LDL-C Targets in Elderly Statin Users After ACS, J Am Heart Assoc; ePub 2018 May 12; Alter, et al

Patient Perspectives on Statin Therapy, Clin Cardiol; ePub 2018 May 10; Brinton