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Bempedoic Acid (ETC-1002)

ATP Citrate Lyase Inhibitor

Review of a First-in-Class Medication with Potential Benefit in Statin-Refractory Cases

Zagelbaum, Nicole K., DO, MPH*; Yandrapalli, Srikanth, MD*; Nabors, Christopher, MD, PhD*; Frishman, William H., MD*,†

doi: 10.1097/CRD.0000000000000218
New Therapy Update

Bempedoic acid (BA; ETC-1002) is a new agent that reduces cholesterol synthesis through inhibition of adenosine triphosphate citrate lyase, an enzyme upstream from 3-hydroxy-3-methylglutaryl-coenzyme A. In animal models, BA also influences fatty acid synthesis, but in humans, its role is limited primarily to lowering low-density lipoprotein cholesterol (LDL-C). In early clinical trials, BA was well tolerated and without major side effects. Alone or in various combinations with atorvastatin and/or ezetimibe, LDL-C lowering ranged from 17% to 64%. In addition, BA lowers levels of non–high-density lipoprotein cholesterol, C-reactive protein, and apolipoprotein B. Statins are first-line agents for primary and secondary prevention of cardiovascular disease. However, muscle-related side effects and other problems such as elevated liver enzymes may limit their use. In addition, LDL-C lowering beyond that provided by statin therapy alone may be needed. BA may be useful in either of these scenarios, as it is relatively free of muscle-related side effects and appears to enhance LDL-C lowering beyond that achieved with statin monotherapy. Phase 3 trials and one outcomes study are currently under way to better define this agent’s potential clinical role.

From the *Department of Medicine

Division of Cardiology, New York Medical College at Westchester Medical Center, Valhalla, NY.

Disclosure: The authors declare no conflict of interest.

Correspondence: Nicole K. Zagelbaum, MD, Department of Medicine, New York Medical College at Westchester Medical Center, 100 Woods Road, Valhalla, NY 10595. E-mail: NicoleZagelbaum@gmail.com.

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