Lipid lowering combination therapy: From prevention to atherosclerosis plaque treatment

Pharmacol Res. 2023 Apr:190:106738. doi: 10.1016/j.phrs.2023.106738. Epub 2023 Mar 20.

Abstract

Statins have contributed to the prevention of numerous atherosclerotic cardiovascular (CV) events and cardiovascular deaths in the past three decades. The benefit of statins is mainly mediated by the lowering of LDLc. According to scientific evidence, the current international guidelines recommend very low LDLc goals in patients at high/very high cardiovascular risk because they are associated with fewer CV events and improvements in atherosclerotic plaques. However, these goals often cannot be obtained with statins alone. Recent RCTs have demonstrated that these CV benefits can also be obtained with nonstatin LDLc-lowering drugs such as PCSK9 inhibitors (alirocumab and evolocumab), ezetimibe and bempedoic acid, while evidence with inclisiran is upcoming. Icosapent ethyl, a lipid metabolism modifier, has also shown an effect on event reduction. Physicians should take advantage of the currently available lipid-lowering therapies, choosing the drug or combination of drugs that is most appropriate for each patient according to his or her CV risk and baseline LDLc concentration. Strategies implementing combination therapies from early stages or even from the outset may increase the number of patients attaining LDLc goals, thereby preventing new CV episodes and improving existing atherosclerotic lesions.

Keywords: Alirocumab; Atherosclerosis treatment; Bempedoic acid; Cardiovascular prevention; Combination therapy; Evolocumab; Ezetimibe; Icosapent ethyl; Inclisiran; Lipid-lowering therapy; Statin; alirocumab; bempedoic acid; evolocumab; ezetimibe; icosapent ethyl; inclisiran.

MeSH terms

  • Anticholesteremic Agents* / therapeutic use
  • Atherosclerosis* / drug therapy
  • Atherosclerosis* / prevention & control
  • Cardiovascular Diseases* / drug therapy
  • Cholesterol, LDL
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Male
  • Plaque, Atherosclerotic* / drug therapy
  • Proprotein Convertase 9 / metabolism

Substances

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