Bempedoic Acid (ETC-1002): ATP Citrate Lyase Inhibitor

Abstract

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.

Statins and Higher Diabetes Mellitus Risk: Incidence, Proposed Mechanisms, and Clinical Implications

“…Furthermore, the use of alternatives like proprotein convertase subtilisin/kexin type 9 serine protease inhibitors, bempedoic acid, and small-interfering RNAs such as inclisiran—agents utilized in patients intolerant to statin therapy—should continue to be evaluated for their unanticipated endocrinological effects. 67 While we await such data, it is important to appropriately prescribe statins when indicated and after a clear patient-centered discussion. Nevertheless, when initiating therapy in those discussed at-risk patient groups, it remains sensible for clinicians to prudently monitor for the potential development of NODM.…”

New approaches to reduce recurrent PCI: to angioplasty and beyond!

“…BA (ETC-1002) (BA) is another new LLT that reduces cholesterol synthesis by inhibiting adenosine triphosphate citrate lyase. 37 The decrease of cholesterol synthesis promotes an upregulation of LDL-receptors and decreases LDL-C. 32 As BA is converted to its active moiety by the long-chain acyl-CoA synthetase-1, an enzyme found only in the liver, BA is believed not to be associated with myalgia, and may be well tolerated in patients with muscle symptoms encountered with statins. 37 A decrease of 20% to 25% in LDL-C would be expected to provide benefits on coronary events, including PCI, and indeed, a signifcant reduction in coronary revascularization was recently seen in CLEAR Outcomes.…”

Diabetic Kidney Disease: Goals for Management, Prevention, and Awareness

“…Another non-statin alternative for dyslipidemia receiving considerable attention is bempedoic acid (BA). Bempedoic acid is an inhibitor of ATP citrate lyase, an enzyme upstream in the cholesterol synthesis pathways [49]. Early clinical trial results showed that bempedoic acid, alone or in conjunction with statins and/or ezetimibe, reduced LDL cholesterol by a range of 17-64% [49].…”

“…Bempedoic acid is an inhibitor of ATP citrate lyase, an enzyme upstream in the cholesterol synthesis pathways [49]. Early clinical trial results showed that bempedoic acid, alone or in conjunction with statins and/or ezetimibe, reduced LDL cholesterol by a range of 17-64% [49]. Another trial tested a combination of bempedoic acid and ezetimibe (BA + EZE) in type 2 diabetes patients with cardiovascular risk [50].…”