Familial Hypercholesterolemia: Challenges for a High-Risk Population: JACC Focus Seminar 1/3

Daein Choi; Waqas A Malick; Wolfgang Koenig; Daniel J Rader; Robert S Rosenson

doi:10.1016/j.jacc.2023.02.038

Familial Hypercholesterolemia: Challenges for a High-Risk Population: JACC Focus Seminar 1/3

J Am Coll Cardiol. 2023 Apr 25;81(16):1621-1632. doi: 10.1016/j.jacc.2023.02.038.

Authors

Daein Choi¹, Waqas A Malick², Wolfgang Koenig³, Daniel J Rader⁴, Robert S Rosenson⁵

Affiliations

¹ Department of Medicine, Mount Sinai Beth Israel, Icahn School of Medicine at Mount Sinai, New York, New York, USA; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
² The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
³ Deutsches Herzzentrum München, Technische Universität München, Munich, Germany; German Centre for Cardiovascular Research, Partner Site Munich Heart Alliance, Munich, Germany; Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany.
⁴ Departments of Medicine and Genetics and the Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁵ The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address: https://twitter.com/DrRSRosenson.

PMID: 37076217
DOI: 10.1016/j.jacc.2023.02.038

Abstract

The availability of statins, ezetimibe, and PCSK9 inhibitors has significantly improved the prognosis of familial hypercholesterolemia (FH). However, a great number of individuals with FH do not achieve guideline-recommended low-density lipoprotein (LDL) cholesterol levels despite maximal lipid-lowering therapy. Novel therapies that lower LDL independent of LDL receptor activity can help mitigate atherosclerotic cardiovascular disease risk in most homozygous FH and many heterozygous FH patients. However, access to novel therapies remains limited for heterozygous FH patients with persistent elevation of LDL cholesterol despite treatment with multiple classes of cholesterol-lowering therapies. Conduction of cardiovascular outcomes clinical trials in patients with FH can be challenging because of difficulty in recruitment and long periods of follow-up. In the future, the use of validated surrogate measures of atherosclerosis may allow for clinical trials with fewer study participants and shorter duration, thereby expediting access to novel treatments for patients with FH.

Keywords: LDL cholesterol; clinical trials; familial hypercholesterolemia; lipid-lowering therapies.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Anticholesteremic Agents* / therapeutic use
Atherosclerosis* / drug therapy
Cholesterol
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
Hyperlipoproteinemia Type II* / drug therapy
Hyperlipoproteinemia Type II* / genetics
Proprotein Convertase 9

Substances

PCSK9 protein, human
Proprotein Convertase 9
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Cholesterol