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LDL-C Lower is Better — EECC MCQ

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ModerateHypertension & Preventive CardiologyLDL-C Lower is BetterEECC

A 55-year-old man with established ASCVD (prior MI) has achieved an LDL-C of 1.1 mmol/L on rosuvastatin 40 mg, ezetimibe, and evolocumab. His cardiologist discusses whether further LDL-C lowering below 1.0 mmol/L provides additional benefit. What does the evidence show?

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Correct answer: C — The relationship between LDL-C lowering and cardiovascular risk reduction is log-linear with no identified lower threshold — lower is better, even below 1.0 mmol/L

The Cholesterol Treatment Trialists (CTT) Collaboration meta-analyses and FOURIER/ODYSSEY subanalyses consistently demonstrate a log-linear relationship between LDL-C reduction and proportional reduction in major cardiovascular events, with no identified lower threshold of benefit or safety concern. Every 1 mmol/L reduction in LDL-C reduces MACE by approximately 22%. The FOURIER trial showed benefit down to LDL-C levels of 0.5 mmol/L without safety signals. The 2019 ESC/EAS Dyslipidaemia Guidelines adopt the principle 'lower is better' and do not set a lower LDL-C safety limit. Concerns about very low LDL-C (cognitive impairment, haemorrhagic stroke) have not been substantiated in randomised trial data.

Reference: ESC/EAS (2019/2025): Guidelines for the Management of Dyslipidaemias