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Lipoprotein Apheresis and Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients With Heterozygous

Vana Kolovou1,2, Niki Katsiki3, Stamatis Makrygiannis4

  • 1Department of Cardiology, 69106Onassis Cardiac Surgery Center, Athens, Greece.

Journal of Cardiovascular Pharmacology and Therapeutics
|July 31, 2020
PubMed

Insights

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) significantly lower LDL-C in patients with heterozygous familial hypercholesterolemia (HeFH) compared to lipoprotein apheresis (LA). PCSK9i therapy may reduce the need for frequent LA sessions.

Area of Science:

  • Cardiology
  • Genetics
  • Pharmacology

Background:

  • Familial hypercholesterolemia (HeFH) is a genetic disorder characterized by high LDL-C levels.
  • Patients with HeFH often require intensive lipid-lowering (LL) therapies, including lipoprotein apheresis (LA).
  • Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a novel class of LL drugs.

Purpose of the Study:

  • To evaluate the lipid-lowering efficacy of PCSK9i in patients with HeFH previously treated with LL drugs and LA.
  • To compare the effectiveness of PCSK9i with LA in managing LDL-C levels in HeFH patients.

Main Methods:

  • A cohort of 17 patients with HeFH, previously treated with statins, ezetimibe, colesevelam, and LA, were switched to PCSK9i therapy (evolocumab or alirocumab).
  • Lipid profiles were assessed before and after LA sessions, and at multiple time points after initiating PCSK9i treatment.
  • The duration of PCSK9i therapy ranged from 3 to 18 months.

Main Results:

  • PCSK9i treatment led to a significant reduction in median TC, LDL-C, and TG levels compared to baseline.
  • Steady-state LDL-C levels achieved with PCSK9i were significantly lower than time-averaged LDL-C levels following LA (100 mg/dL vs. 155 mg/dL).
  • A substantial proportion of patients (46.1%) achieved LDL-C <70 mg/dL with PCSK9i therapy.

Conclusions:

  • PCSK9i demonstrate superior and more consistent LDL-C reduction over time compared to the transient effects of LA in HeFH patients.
  • PCSK9i therapy holds potential to decrease the frequency of LA sessions required for managing HeFH.
  • Larger clinical trials are warranted to fully elucidate the implications of PCSK9i in patients with a history of LA.
Abstract

Keywords:
PCSK9 inhibitorsheterozygous familial hypercholesterolemialipoprotein apheresisproprotein convertase subtilisin/kexin type 9 inhibitorsstatins

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