Bempedoicacid
ATP-citrate lyase inhibitor · “The statin-intolerant solution”
The Clinical Case
Female, 71 yo. Established ASCVD. LDL 3.2 mmol/L. Has tried four statins — all caused confirmed disabling myalgia on rechallenge. Refuses injectable therapies. Lipidologist prescribes a novel oral drug (approved 2020) that blocks the mevalonate pathway upstream of HMG-CoA reductase, is activated only in hepatocytes, cannot cause myopathy, and whose 2023 CVOT trial demonstrated cardiovascular benefit in statin-intolerant patients.
The Answer
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Clinical Pearl
Mechanism: Inhibits ATP-citrate lyase (ACL) — upstream of HMG-CoA reductase in mevalonate pathway; prodrug activated by hepatic ACSVL1 only
All Hints
Mechanism: Inhibits ATP-citrate lyase (ACL) — upstream of HMG-CoA reductase in mevalonate pathway; prodrug activated by hepatic ACSVL1 only
Muscle safety: ACSVL1 enzyme absent in skeletal muscle → no myopathy; specifically approved for statin-intolerant patients
Efficacy: LDL↓ ~18–25% alone; available as fixed-dose combination with ezetimibe (↓ LDL ~38%)
CLEAR Outcomes: 2023 CVOT: 13% RRR in MACE in statin-intolerant patients — first CV outcomes evidence for this drug class
Adverse effects: Raises uric acid (caution in gout); mild ↑creatinine (non-nephrotoxic); tendon rupture signal in elderly patients
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