Efficacy and safety of add on therapies in patients with hypercholesterolemia undergoing statin therapy

Expert Opin Pharmacother. 2020 Dec;21(17):2137-2151. doi: 10.1080/14656566.2020.1801638. Epub 2020 Aug 9.

Abstract

Introduction: Statins are the first-line treatment to reduce cardiovascular (CV) events, mainly by reducing low-density-lipoprotein cholesterol (LDL-C), but many patients need additional treatments to reach the current lipid goals.

Areas covered: Herein, the authors review the published literature on the efficacy and safety of the therapies that are most often added to statins to achieve lipid targets.

Expert opinion: Ezetimibe is usually the first additional treatment to achieve LDL-C targets. It reduces LDL-C by about a further 20% and has an excellent safety and tolerability profile. The monoclonal antibody proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, evolocumab, and alirocumab, can reduce LDL-C by ≥50% when added to statins and they also have a well-established safety and tolerability record. The recently approved bempedoic acid is well tolerated and appears to be free of skeletal muscle-related problems, but the CV outcome study with this drug has not been completed. Inclisiran, a small-interfering RNA targeting PCSK9 is at an advanced stage of development and the available data indicate a satisfactory safety profile and LDL-C lowering efficacy similar to the PCSK9 monoclonal antibodies with the advantage of less frequent administration.

Keywords: Alirocumab; bempedoic acid; evolocumab; ezetimibe; icosapent ethyl; inclisiran; proprotein convertase subtilisin/kexin type 9 inhibitors; statins.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Cholesterol, LDL / blood
  • Clinical Trials as Topic
  • Drug Therapy, Combination
  • Ezetimibe / administration & dosage
  • Ezetimibe / adverse effects
  • Ezetimibe / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy*
  • PCSK9 Inhibitors
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • PCSK9 Inhibitors
  • PCSK9 protein, human
  • Ezetimibe
  • evolocumab
  • alirocumab