Targeting low-density lipoprotein cholesterol with PCSK9 inhibitors

Intern Med J. 2017 Aug;47(8):856-865. doi: 10.1111/imj.13451.

Abstract

Over the past quarter century, clinical trials have consistently demonstrated that lowering levels of low-density lipoprotein cholesterol (LDL-C) with statins reduces the rate of major adverse cardiovascular events. However, the findings that many patients continue to experience events or harbour inappropriately high LDL-C levels despite intensive statin therapy and the clinical reality of statin intolerance suggests that additional therapeutic strategies are required in order to achieve more effective reductions in cardiovascular risk. The emergence of inhibitory monoclonal antibodies targeted against proprotein convertase subtilisin kexin type 9 (PCSK9) provides a novel approach to reducing LDL-C levels. The current experience of PCSK9 inhibitors and implications for clinical use and cost effectiveness will be reviewed.

Keywords: PCSK9 inhibitors; atherosclerosis; cardiovascular risk; lipids.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Anticholesteremic Agents / pharmacology
  • Anticholesteremic Agents / therapeutic use*
  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / etiology
  • Cardiovascular Diseases* / genetics
  • Cardiovascular Diseases* / prevention & control
  • Cholesterol, LDL / blood
  • Cholesterol, LDL / drug effects*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • PCSK9 Inhibitors*
  • Randomized Controlled Trials as Topic

Substances

  • Antibodies, Monoclonal
  • Anticholesteremic Agents
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • PCSK9 Inhibitors
  • PCSK9 protein, human