EAS 2020 — Lipid goals and therapeutic approaches from the EAS standpoint


  • Pavankumar Kamat
  • Conference Reports
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Takeaway

  • Dr Chris Packard, UK, and Dr Alberico Luigi Catapano, Italy, discuss the targets and goals for low-density lipoprotein-cholesterol (LDL-C) reduction and the therapeutic approaches to achieve them from the European Atherosclerosis Society (EAS) standpoint.
  • The EAS emphasizes that there is no defined LDL-C level below which risk reduction ceases or safety is compromised.

Key points

  • LDL-C is a major independent risk factor for atherosclerotic cardiovascular disease (ASCVD).
  • Genetic analysis points to a causal association between LDL-C and ASCVD risk.
  • The EAS uses evaluation of the scientific framework of the relationship between LDL-C and atherosclerosis to define LDL-C goals.
  • Evidence shows that relative risk reduction is proportional to the absolute reduction in LDL-C, with no indication of a balancing act to be maintained between safety and efficacy.
  • In the ODYSSEY outcomes trial, a risk reduction was observed in the lowest vs the highest tertiles of LDL-C.
  • In FOURIER trial, where the entire population was divided as per achieved LDL-C levels from 4.5 mmol/L to
  • Meta-regression analysis of data from trials of statin vs placebo, more vs less intense statin therapy and combination therapy with ezetimibe revealed a rule of thumb that every 1.0 mmol/L reduction in LDL-C translates into a 22% risk reduction.
  • Safety of profound (
  • Human genetic studies indicate that with a double loss of function in proprotein convertase subtilisin/kexin type 9 (PCSK9), LDL-C level is 0.36 mmol/L over a lifetime.
  • There is a very low incidence of ASCVD and no adverse outcomes.
  • Adverse event profiles of evolocumab in FOURIER, alirocumab in ODYSSEY OUTCOMES, anacetrapib in REVEAL and ezetimibe in IMPROVE-IT did not indicate a safety disbenefit.
  • Based on these findings, the guidelines say that "no level of LDL-C below which benefit ceases or harm occurs has been defined."
  • Goals for LDL-C (2019 guidelines):
    • Very high-risk:
    • High-risk:
    • Moderate-risk:
    • Low-risk:
  • Recommendations for pharmacological LDL-C reduction (2019 guidelines):
    • High-intensity statin up to the highest tolerated dose can be prescribed to reach the goals defined for specific risk levels (Class I).
    • If goals are not achieved with the maximum tolerated statin dose, a combination with ezetimibe is recommended (Class I).
    • For primary prevention in very high-risk patients without familial hypercholesterolemia (FH), if the LDL-C goal is not achieved with statin plus ezetimibe, a combination with PCSK9 inhibitor may be considered (Class IIb).
    • For secondary prevention in very high-risk patients, if the LDL-C goal is not achieved with statin plus ezetimibe, a combination with PCSK9 inhibitor is recommended (Class I).
    • In very high-risk patients with FH, if the LDL-C goal is not achieved with statin plus ezetimibe, a combination with PCSK9 inhibitor is recommended (Class I).
    • If statin-based therapy is not tolerated at any dose, ezetimibe should be considered (Class IIa) or a PCSK9 inhibitor added to ezetimibe may also be considered (Class IIb).
    • A combination of statin and bile acid sequestrant may be considered if LDL-C goals are not achieved (Class IIb).