Elevated low-density lipoprotein cholesterol (LDL-C) is a principally modifiable cause of atherosclerotic cardiovascular disease; accordingly, recent European and US multisociety dyslipidaemia guidelines emphasise the importance of lowering LDL-C to reduce cardiovascular risk. This review provides perspectives on established and emerging agents that reduce LDL-C to help providers synthesize the abundance of new evidence related to prevention of cardiovascular disease. We provide hypothetical cases of patients with different cardiovascular risk factors and medical histories to illustrate application of current lipid-lowering guidelines in various clinical settings. As a core focus of preventive therapy, both European and US lipid management guidelines emphasise the importance of identifying patients at very high cardiovascular risk and treating to achieve LDL-C levels as low as possible, with European guidelines setting a goal of <1.4 mmol/L (<55 mg/dL) in patients with very high-risk cardiovascular disease.1

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Cardiovascular disease caused by atherosclerosis causes significant morbidity and mortality, which can be improved by controlling risk factors through lifestyle interventions and lipid-lowering medications. The U.S. Department of Veterans Affairs and Department of Defense (VA/DoD) have updated recommendations for evaluation and management of dyslipidemia to prevent cardiovascular disease.2

Key Points for Practice 2

  • In primary prevention, moderate-dose statins are recommended when treatment is indicated.
  • In secondary prevention, moderate-dose statins are recommended with intensification by increasing statin dose, adding ezetimibe, or adding a PCSK9 inhibitor in higher-risk patients.
  • Because cholesterol values are stable over 10 years, new measurements are not needed for each risk assessment.


  1. D. Atar et al. Atherosclerosis 319 (2021) 51-61.
  2. Am Fam Physician. 2021 Apr 15;103(8):507-509.