Bempedoic Acid: ATP-Citrate Lyase Inhibitor for LDL-C Reduction
Bempedoic acid (Nexletol) is an oral ATP-citrate lyase (ACL) inhibitor that reduces hepatic cholesterol synthesis upstream of HMG-CoA reductase. Because it requires activation by an enzyme (ACSVL1) present only in the liver, it does not cause myopathy.
Indicated for patients with primary hypercholesterolaemia or mixed dyslipidaemia who are statin-intolerant or cannot achieve LDL-C targets on maximally tolerated statin therapy.
Mechanism of Action
Bempedoic acid inhibits ACL, blocking the conversion of citrate to acetyl-CoA and oxaloacetate in the liver — thereby reducing the substrate available for cholesterol synthesis. This upregulates LDL receptors, increasing LDL clearance. The liver-specific activation avoids skeletal muscle effects.
Indications & Use
Adjunct to diet and maximally tolerated statin therapy in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia. Also used as monotherapy in statin-intolerant patients.
Dosage
180 mg once daily, with or without food. Can be combined with ezetimibe (fixed-dose combination Nexlizet available). No dose adjustment required for renal impairment. Avoid in severe hepatic impairment.
Side Effects
Hyperuricaemia and gout flares (most common serious side effect — due to bempedoic acid inhibiting renal urate transporters). Tendon rupture risk (monitor; avoid in tendon disorders). Elevated liver enzymes, anaemia, back pain.
Drug Interactions
Simvastatin/pravastatin: bempedoic acid inhibits OATP1B1, increasing their plasma levels — do not exceed simvastatin 20 mg or pravastatin 40 mg. Rosuvastatin: avoid combination at doses >20 mg.
Contraindications
Hypersensitivity to bempedoic acid. Not recommended in severe hepatic impairment. Use with caution in patients with history of gout or tendon disorders.
Frequently Asked Questions
Why does bempedoic acid not cause muscle pain like statins?
Bempedoic acid requires activation by the enzyme ACSVL1, which is only present in the liver. Skeletal muscle lacks this enzyme, so the drug remains inactive there, avoiding statin-like myopathy.
How much does bempedoic acid lower LDL-C?
In clinical trials, bempedoic acid alone reduced LDL-C by approximately 15–25%. Combined with ezetimibe (Nexlizet), reductions of 35–40% are achievable. It reduces cardiovascular events in statin-intolerant high-risk patients (CLEAR Outcomes trial).
Can I take bempedoic acid with statins?
Yes — it is specifically indicated as add-on to statin therapy. However, statin doses may need adjustment (simvastatin max 20 mg, pravastatin max 40 mg) due to drug interactions increasing statin exposure.
References
- CLEAR Outcomes Trial (bempedoic acid)
- ESC Dyslipidaemia Guidelines 2019
- EMA product information Nexletol
Medical Disclaimer: This information is for educational purposes only and does not replace professional medical advice.