Intervention
Bempedoic Acid
Last updated Sat May 30 2026 00:00:00 GMT+0000 (Coordinated Universal Time)
RCT evidence— CLEAR Outcomes
What it is
Bempedoic acid is a prodrug activated to its active metabolite (ETC-1002) by ACSVL1, which is present in liver but not in skeletal muscle. The activated form inhibits ATP-citrate lyase (ACL) in the cholesterol biosynthesis pathway upstream of HMG-CoA reductase (the statin target).
Why it matters
- LDL-lowering without statin-style muscle effects in patients who are statin-intolerant.
- CLEAR Outcomes (2023): in statin-intolerant patients, bempedoic acid reduced major cardiovascular events 13% vs placebo over ~3.4 years.
- Often combined fixed-dose with ezetimibe (Nexlizet) for stronger LDL effect.
Side-effect profile
- Hyperuricaemia — can precipitate gout in susceptible patients.
- Modest increase in tendon disorders.
- Gallstone risk.
- No muscle effects, no glycaemic effects.
Place in therapy
After statins ± ezetimibe in adults with remaining cardiovascular risk who can’t tolerate higher statin doses. Used before PCSK9 inhibitors in many algorithms due to lower cost and oral dosing.
Related entries
Statins, Ezetimibe, PCSK9 inhibitors, Cardiovascular disease.
References
- Nissen, S. E. et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients (CLEAR Outcomes). N. Engl. J. Med. 388, 1353–1364 (2023).