Lipid Lowering Therapy: An Era Beyond Statins

Curr Probl Cardiol. 2022 Dec;47(12):101342. doi: 10.1016/j.cpcardiol.2022.101342. Epub 2022 Jul 31.


Dyslipidemia, specifically elevated low-density lipoprotein (LDL) cholesterol levels, causes atherosclerotic cardiovascular disease (ASCVD) and increases the risk of myocardial infarction and stroke. Statins, a class of drugs that exert their effects by inhibiting HMG-CoA reductase, a key enzyme in the synthesis of cholesterol, have been the mainstay of therapy for the primary prevention of cardiovascular disease and lipids reduction. Statins are associated with side effects, most commonly myopathy and myalgias, despite their proven efficacy. This review explores non-statin lipid-lowering therapies and examines recent advances and emerging research. Over the previous decades, several lipid-lowering therapies, both as monotherapy and adjuncts to statin therapy and lipid-targeting gene therapy, have emerged, thus redefining how we treat dyslipidemia. These drugs include Bile acids sequestrants, Fibrates, Nicotinic acid, Ezetimibe, Bempedoic acid, Volanesoren, Evinacumab, and the PCSK 9 Inhibitors Evolocumab and Alirocumab. Emerging gene-based therapy includes Small interfering RNAs, Antisense oligonucleotides, Adeno-associated virus vectors, CRISPR/Cas9 based therapeutics, and Non-coding RNA therapy. Of all these therapies, Bempedoic acid works most like statins by working through a similar pathway to decrease cholesterol levels. However, it is not associated with myopathy. Overall, although statins continue to be the gold standard, non-statin therapies are set to play an increasingly important role in managing dyslipidemia.

Publication types

  • Review

MeSH terms

  • Anticholesteremic Agents* / adverse effects
  • Cardiovascular Diseases* / etiology
  • Cardiovascular Diseases* / prevention & control
  • Cholesterol / therapeutic use
  • Cholesterol, LDL / therapeutic use
  • Dyslipidemias* / drug therapy
  • Ezetimibe / pharmacology
  • Ezetimibe / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
  • Anticholesteremic Agents
  • Cholesterol, LDL
  • Ezetimibe
  • Cholesterol