EAS 2020 — New concept of lipid lowering: start early and aggressively


  • Antara Ghosh
  • Conference Reports
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Takeaway

  • Professor François Mach reviews the modern concept of lipid lowering which involves initiating lipid-lowering therapy at the earliest and treating aggressively to achieve the lowest possible target of low-density lipoprotein-cholesterol (LDL-C).
  • Greater use of combination lipid-lowering therapies is emphasized to reach the lipid goals stated by the 2019 European Society of Cardiology/European Atherosclerosis Society guidelines, thereby reducing the future risk for cardiovascular events.

Key highlights

  • Evidence from the last 10 years has shown that lower LDL-C is better, but even lower is even better.
  • Recent evidence shows that lower LDL-C levels (close to 1.4-1.5 mmol/L) achieved with intensive lipid lowering are associated with a massive reduction in the future risk for cardiovascular events:
    • CTT meta-analysis (high-intensity vs standard statin): relative risk (RR) per mmol/L of LDL-C reduction, 0.71; 95% CI, 0.56-0.91;
    • IMPROVE-IT (ezetimibe+statin vs statin): RR, 0.94; 95% CI, 0.89-0.99;
    • FOURIER (evolocumab+high-intensity statin±ezetimibe vs high-dose statin±ezetimibe): RR, 0.85; 95% CI, 0.79-0.92; and
    • ODYSSEY OUTCOMES (alirocumab+high-dose statin±ezetimibe vs high-dose statin±ezetimibe): RR, 0.85; 95% CI, 0.78-0.93.
  • Despite LDL-C
  • Based on these findings, the 2019 guidelines classified patients into different risk categories and defined new LDL-C goals for each category:
    • Very high risk:
    • High risk:
    • Moderate risk:
    • Low risk:
  • Updated recommendations included:
    • adding ezetimibe to maximally tolerated statin dose if goals were not achieved (Class IB).
    • adding a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) to maximally tolerated statin+ezetimibe for secondary prevention in very high-risk patients not achieving their goals (Class IA); and
    • adding PCSK9i to maximally tolerated statin+ezetimibe in very high-risk patients with familial hypercholesterolemia not achieving their goals (Class IC).
  • In FOURIER trial, a significant and consistent risk reduction was observed with a reduction in LDL-C (P=.0012) without any safety concerns (LDL-C mmol/L vs ≥2.6 mmol/L; adjusted HR for serious adverse events, 0.96; 95% CI, 0.81-1.13; P=.63).
  • In patients with recent myocardial infarction, evolocumab reduced the risk by 19% for primary endpoint and by 25% for cardiovascular death/myocardial infarction/stroke.
  • In EVOPACS trial, 90.1% of patients with acute coronary syndrome achieved the target LDL-C with in-hospital initiation of evolocumab+high-intensity statins vs 10.7% with placebo.
  • Based on all data, the 2019 guideline updates for patients at very high-risk with acute coronary syndrome includes:
    • adding ezetimibe if LDL-C goals are not achieved after 4-6 weeks with maximally tolerated statin (Class IB);
    • adding PCSK9i if LDL-C goals are not achieved after 4-6 weeks with statin+ezetimibe combination (Class IB); and
    • considering PCSK9i early after the event (if possible, during hospitalization) in patients having LDL-C above the target despite statin+ezetimibe therapy (Class IIa-C).