Evaluation of Major Cardiovascular Events in Participants With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated With Bempedoic Acid (ETC-1002) or Placebo

Summary

The purpose of this study is to determine if treatment with bempedoic acid (ETC-1002) versus placebo decreases the risk of cardiovascular events in participants who have or are at high risk for cardiovascular disease and are statin intolerant.

Timeline

Start

2016-12-22

Primary completion

2022-11-07

Completion

2022-11-07

Publications

• Background Pinkosky SL, Newton RS, Day EA, Ford RJ, Lhotak S, Austin RC, Birch CM, Smith BK, Filippov S, Groot PHE, Steinberg GR, Lalwani ND. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun. 2016 Nov 28;7:13457. doi: 10.1038/ncomms13457.
• Background Bilen O, Ballantyne CM. Bempedoic Acid (ETC-1002): an Investigational Inhibitor of ATP Citrate Lyase. Curr Atheroscler Rep. 2016 Oct;18(10):61. doi: 10.1007/s11883-016-0611-4.
• Background Thompson PD, MacDougall DE, Newton RS, Margulies JR, Hanselman JC, Orloff DG, McKenney JM, Ballantyne CM. Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance. J Clin Lipidol. 2016 May-Jun;10(3):556-67. doi: 10.1016/j.jacl.2015.12.025. Epub 2016 Jan 6.
• Background Thompson PD, Rubino J, Janik MJ, MacDougall DE, McBride SJ, Margulies JR, Newton RS. Use of ETC-1002 to treat hypercholesterolemia in patients with statin intolerance. J Clin Lipidol. 2015 May-Jun;9(3):295-304. doi: 10.1016/j.jacl.2015.03.003. Epub 2015 Mar 19.
• Background Nicholls S, Lincoff AM, Bays HE, Cho L, Grobbee DE, Kastelein JJ, Libby P, Moriarty PM, Plutzky J, Ray KK, Thompson PD, Sasiela W, Mason D, McCluskey J, Davey D, Wolski K, Nissen SE. Rationale and design of the CLEAR-outcomes trial: Evaluating the effect of bempedoic acid on cardiovascular events in patients with statin intolerance. Am Heart J. 2021 May;235:104-112. doi: 10.1016/j.ahj.2020.10.060. Epub 2020 Oct 24.
• Background Nissen SE, Lincoff AM, Brennan D, Ray KK, Mason D, Kastelein JJP, Thompson PD, Libby P, Cho L, Plutzky J, Bays HE, Moriarty PM, Menon V, Grobbee DE, Louie MJ, Chen CF, Li N, Bloedon L, Robinson P, Horner M, Sasiela WJ, McCluskey J, Davey D, Fajardo-Campos P, Petrovic P, Fedacko J, Zmuda W, Lukyanov Y, Nicholls SJ; CLEAR Outcomes Investigators. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. N Engl J Med. 2023 Apr 13;388(15):1353-1364. doi: 10.1056/NEJMoa2215024. Epub 2023 Mar 4.
• Background Nissen SE, Menon V, Nicholls SJ, Brennan D, Laffin L, Ridker P, Ray KK, Mason D, Kastelein JJP, Cho L, Libby P, Li N, Foody J, Louie MJ, Lincoff AM. Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients. JAMA. 2023 Jul 11;330(2):131-140. doi: 10.1001/jama.2023.9696.
• Spiazzi BF, Brennan D, Zingano CP, Powell HA, Nicholls SJ, Nissen SE, Laffin LJ. Bempedoic Acid and Venous Thromboembolism Risk Among Statin-Intolerant Patients: A Post Hoc Analysis of the CLEAR Outcomes Randomized Clinical Trial. JAMA Cardiol. 2026 Jul 1;11(7):659-663. doi: 10.1001/jamacardio.2026.1208.
• Naderi S, Brennan D, Li N, Lincoff AM, Nicholls SJ, Nissen SE, Plutzky J, Powell HA, Robinson P, Cho L. Sex Differences in Statin Intolerance: Insights From the CLEAR Outcomes Trial. Clin Cardiol. 2026 Apr;49(4):e70288. doi: 10.1002/clc.70288.
• Nicholls SJ, Ray KK, Lincoff AM, Sarnes E, Gillard KK, Bloedon L, Migliaccio-Walle K, Elsea D, Nissen SE. Cost-Effectiveness of Bempedoic Acid in High Cardiovascular Risk Patients with Statin Intolerance: An Analysis of the CLEAR Outcomes Trial. Am J Cardiovasc Drugs. 2026 Jan;26(1):59-70. doi: 10.1007/s40256-025-00753-w. Epub 2025 Aug 20.
• Laufs U, Lincoff AM, Nicholls SJ, Li N, Bloedon L, Sasiela WJ, Powell HA, Herout PM, Thompson PD, Nissen SE. Characteristics and outcomes of patients with and without statin-associated muscle symptoms treated with bempedoic acid in the CLEAR Outcomes trial. J Clin Lipidol. 2025 Mar-Apr;19(2):337-347. doi: 10.1016/j.jacl.2024.12.014. Epub 2024 Dec 25.
• Bays HE, Bloedon L, Brennan D, Lei L, Lincoff AM, Nicholls SJ, Plutzky J, Powell HA, Nissen SE. Bempedoic Acid for Prevention of Cardiovascular Events in People With Obesity: A CLEAR Outcomes Subset Analysis. J Am Heart Assoc. 2025 Feb 18;14(4):e037898. doi: 10.1161/JAHA.124.037898. Epub 2025 Feb 8.
• Lincoff AM, Ray KK, Sasiela WJ, Haddad T, Nicholls SJ, Li N, Cho L, Mason D, Libby P, Goodman SG, Nissen SE. Comparative Cardiovascular Benefits of Bempedoic Acid and Statin Drugs. J Am Coll Cardiol. 2024 Jul 9;84(2):152-162. doi: 10.1016/j.jacc.2024.04.048.
• Ray KK, Nicholls SJ, Li N, Louie MJ, Brennan D, Lincoff AM, Nissen SE; CLEAR OUTCOMES Committees and Investigators. Efficacy and safety of bempedoic acid among patients with and without diabetes: prespecified analysis of the CLEAR Outcomes randomised trial. Lancet Diabetes Endocrinol. 2024 Jan;12(1):19-28. doi: 10.1016/S2213-8587(23)00316-9. Epub 2023 Dec 4.
• Ridker PM, Lei L, Louie MJ, Haddad T, Nicholls SJ, Lincoff AM, Libby P, Nissen SE; CLEAR Outcomes Investigators. Inflammation and Cholesterol as Predictors of Cardiovascular Events Among 13 970 Contemporary High-Risk Patients With Statin Intolerance. Circulation. 2024 Jan 2;149(1):28-35. doi: 10.1161/CIRCULATIONAHA.123.066213. Epub 2023 Nov 6.

Drugs

Indications