Novel emerging therapies in atherosclerosis targeting lipid metabolism

Expert Opin Investig Drugs. 2020 Jun;29(6):611-622. doi: 10.1080/13543784.2020.1764937. Epub 2020 May 22.

Abstract

Introduction: Recent years have brought significant developments in lipid and atherosclerosis research. Although statins are a cornerstone in hyperlipidemia management, new non-statin therapies have had an impact. The reduction of low-density lipoprotein cholesterol (LDL-C) further translates into the lowering of cardiovascular mortality. Additionally, lipid research has progressed beyond LDL-C reduction and this has brought triglyceride (TG) and other apoprotein-B containing lipids into focus.

Areas covered: Inclisiran and pemafibrate, with expected approval soon, come under the spotlight. We discuss other therapeutics such as lomitapide, mipomersen, volanesorsen, and evinacumab and newly approved non-statin-based therapies such as ezetimibe, icosapent ethyl (IPE), and bempedoic acid.

Expert opinion: New options now exist for the prevention of atherosclerosis in patients that are not optimized on statin therapy. Multiple guidelines endorse ezetimibe, PCSK9 inhibitors, bempedoic, and IPE as add-on therapy. Recently approved bempedoic acid/ezetimibe combination might gain popularity among clinicians. Inclisiran and pemafibrate show promise in the reduction of LDL-C and TG, respectively, and results are pending in cardiovascular outcome trials. Combination strategies could improve outcomes, but the challenge will be balancing cost and selecting the correct patient population for each treatment modality to maximize benefit with the fewest medications.

Keywords: Atherosclerosis; CLEAR harmony; EVAPORATE; FOURIER; IMPROVE-IT; ODYSSEY; ORION-10; PCSK9 inhibitors; REDUCE-IT; bempedoic acid; evinacumab; inclisiran; lomitapide; pemafibrate; pemfibrate.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / pathology
  • Cardiovascular Diseases / prevention & control
  • Cholesterol, LDL / blood
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hyperlipidemias / complications
  • Hyperlipidemias / drug therapy
  • Hypolipidemic Agents / pharmacology*
  • Lipid Metabolism / drug effects*

Substances

  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents