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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.

Citation:

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.

This Week's Must Reads

Evolocumab Lowers LDL-C in Patient Subgroups, Clin Cardiol; 2018 Oct 21; Stroes, Robinson, et al

Is Further Lowering of LDL-C in Patients Safe?, JAMA Cardiol; 2018 Sep; Sabatine, Wiviott, et al

Effects of Primary Prevention on CVD Event Risk, J Manag Care Spec Pharm; 2018 Nov; Han, et al

FH Patients with Diabetes at Elevated Risk for CVD, J Clin Lipidol; ePub 2018 Sep 17; Paquette, et al

Long-Term Benefit to Statin Eligibility, JAMA Cardiol; ePub 2018 Oct 24; Thanassoulis, et al

Must Reads in Hypercholesterolemia

Evolocumab Lowers LDL-C in Patient Subgroups, Clin Cardiol; 2018 Oct 21; Stroes, Robinson, et al

Is Further Lowering of LDL-C in Patients Safe?, JAMA Cardiol; 2018 Sep; Sabatine, Wiviott, et al

Effects of Primary Prevention on CVD Event Risk, J Manag Care Spec Pharm; 2018 Nov; Han, et al

FH Patients with Diabetes at Elevated Risk for CVD, J Clin Lipidol; ePub 2018 Sep 17; Paquette, et al

Long-Term Benefit to Statin Eligibility, JAMA Cardiol; ePub 2018 Oct 24; Thanassoulis, et al