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Bempedoic Acid — EECC MCQ

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ModerateCoronary Artery DiseaseBempedoic AcidEECC

A 55-year-old woman with established CAD asks about bempedoic acid. She has statin-associated muscle symptoms (SAMS) and cannot tolerate any statin. Her LDL-C is 3.5 mmol/L on ezetimibe alone. What is bempedoic acid's mechanism and evidence?

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Correct answer: E — Bempedoic acid inhibits ATP citrate lyase (upstream of HMG-CoA reductase), reducing cholesterol synthesis; the CLEAR Outcomes trial demonstrated cardiovascular event reduction in statin-intolerant patients — it does not cause myalgia as it is a prodrug activated only in the liver, not skeletal muscle

Bempedoic acid inhibits ATP citrate lyase (ACL), an enzyme upstream of HMG-CoA reductase in the cholesterol synthesis pathway. It is a prodrug that requires activation by ACSVL1 (acyl-CoA synthetase), which is expressed in liver but NOT in skeletal muscle — explaining the absence of myalgia (a key advantage in SAMS patients). The CLEAR Outcomes trial (2023) demonstrated that bempedoic acid 180 mg daily reduced MACE by 13% in statin-intolerant patients. LDL-C reduction is ~18-25% as monotherapy, ~38% combined with ezetimibe. The ESC/EAS Dyslipidaemia Guidelines include bempedoic acid in the treatment algorithm for patients unable to achieve LDL-C targets, particularly those with statin intolerance. Side effects include hyperuricaemia and tendon rupture.

Reference: ESC/EAS Dyslipidaemia Guidelines; CLEAR Outcomes Trial