Low-density lipoprotein cholesterol lowering treatment: the current approach

Lipids Health Dis. 2020 May 6;19(1):85. doi: 10.1186/s12944-020-01275-x.

Abstract

In the last 50 years, several clinical and epidemiological studies during have shown that increased levels of low-density lipoprotein cholesterol (LDLc) are associated with the development and progression of atherosclerotic lesions. The discovery of β-Hydroxy β-methylglutaryl-CoA reductase inhibitors (statins), that possess LDLc-lowering effects, lead to a true revolution in the prevention and treatment of cardiovascular diseases. Statins remain the cornerstone of LDLc-lowering therapy. Lipid-lowering drugs, such as ezetimibe and bile acid sequestrants, are prescribed either in combination with statins or in monotherapy (in the setting of statin intolerance or contraindications to statins). Microsomal triglyceride transfer protein inhibitors and protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are other drug classes which have been investigated for their potential to decrease LDLc. PCSK9 have been approved for the treatment of hypercholesterolemia and for the secondary prevention of cardiovascular events. The present narrative review discusses the latest (2019) guidelines of the European Atherosclerosis Society/European Society of Cardiology for the management of dyslipidemia, focusing on LDLc-lowering drugs that are either already available on the market or under development. We also consider "whom, when and how" do we treat in terms of LDLc reduction in the daily clinical practice.

Keywords: Atherosclerosis; Dyslipidemia; LDL-cholesterol; PCSK9 inhibitors; Statins.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Anticholesteremic Agents / therapeutic use*
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control*
  • Benzimidazoles / therapeutic use
  • Bile Acids and Salts / antagonists & inhibitors
  • Bile Acids and Salts / metabolism
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cholesterol, LDL / antagonists & inhibitors*
  • Cholesterol, LDL / metabolism
  • Dicarboxylic Acids / therapeutic use
  • Europe
  • Ezetimibe / therapeutic use
  • Fatty Acids / therapeutic use
  • Gene Expression
  • Guidelines as Topic
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / genetics
  • Hypercholesterolemia / metabolism
  • Hypercholesterolemia / pathology
  • PCSK9 Inhibitors
  • Proprotein Convertase 9 / genetics
  • Proprotein Convertase 9 / metabolism
  • RNA, Small Interfering / therapeutic use

Substances

  • ALN-PCS
  • Antibodies, Monoclonal, Humanized
  • Anticholesteremic Agents
  • BMS201038
  • Benzimidazoles
  • Bile Acids and Salts
  • Carrier Proteins
  • Cholesterol, LDL
  • Dicarboxylic Acids
  • Fatty Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • PCSK9 Inhibitors
  • RNA, Small Interfering
  • microsomal triglyceride transfer protein
  • 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Ezetimibe
  • evolocumab
  • alirocumab