Persons at high risk of cardiovascular disease can be effectively identified from a measurement of their serum cholesterol. Despite of effectiveness of statins in the treatment of lipid disorders like hyper cholesterolemia, hyperlipidaemia, atherosclerosis, Residual risk still exists, and some studies, additional drugs were added to statin therapy have been mainly negative or the outcomes were very modest. Bempedoic acid is a novel oral drug, which has been increasingly researched to play an important role in lowering LDL cholesterol. Some patients inability to tolerate statins because of muscle symptoms contributes to uncontrolled cholesterol levels, insufficient cardiovascular risk reduction, patients with familial hypercholesterolemia, fail to achieve LDL-C targets with statins alone, and others are either statin intolerant or tolerate only suboptimal low doses. The review covers the current state of knowledge on the mechanism of action of bempedoic acid (ETC-1002) and results from recent clinical studies.

Keywords: Cardiovascular diseases, Hypercholesterolemia, Hyperlipidaemia, Atherosclerosis, Bempedoic acid.

1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation. 2015; 131:e29–322. pmid:25520374.
2. Ference BA, Yoo W, Alesh I, Mahajan N, Mirowska KK, Mewada A, et al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. J Am CollCardiol. 2012; 60: 2631–9. pmid:23083789.
3. Strilchuk L, Fogacci F, Cicero AF. Safety and tolerability of injectable lipid-lowering drugs: an update of clinical data. Expert Opin Drug Saf. 2019; 18: 611–21. pmid:31100030.
4. Ruscica M, Banach M, Sahebkar A, Corsini A, Sirtori CR. ETC-1002 (bempedoic acid) for the management of hyperlipidemia: from preclinical studies to phase 3 trials.
5. Beigneux AP, Kosinski C, Gavino B, Horton JD, Skarnes WC, Young SG. ATP-citrate lyase deficiency in the mouse. J Biol Chem. 2004; 279:9557–64. pmid:14662765
6. Berkhout TA, Havekes LM, Pearce NJ, Groot PH. The effect of (-)-hydroxycitrate on the activity of the low-density-lipoprotein receptor and 3-hydroxy-3-methylglutaryl-CoA reductase levels in the human hepatoma cell line Hep G2. Biochem J. 1990; 272: 181–6. pmid:2176080
7. Saeed A, Ballantyne CM. Bempedoic acid (ETC-1002): a current review. Cardiol Clin. 2018; 36: 257–64. pmid: 29609755.
8. Pinkosky SL, Newton RS, Day EA, Ford RJ, Lhotak S, Austin RC, et al. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun. 2016; 7: 13457. pmid:27892461.
9. Laufs U, Banach M, Mancini GBJ, Gaudet D, Bloedon LT, Sterling LR, et al. Efficacy and safety of bempedoic acid in patients with hypercholesterolemia and statin intolerance. J Am Heart Assoc. 2019;8: e011662. pmid:30922146.
10. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009; 339:b2535. pmid:19622551.
11. Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions. Chichester (UK): John Wiley & Sons; 2008.
12. Sahebkar A, Pirro M, Banach M, Mikhailidis DP, Atkin SL, Cicero AFG. Lipid-lowering activity of artichoke extracts: a systematic review and meta-analysis. Crit Rev Food SciNutr. 2018;58: 2549–56. pmid:28609140.
13. Virani AA, Alonso A, Benjamin EJ, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2020 update: a report from the American Heart Association. 2020;141: e139–e596. doi: 10.1161/CIR.0000000000000757.
14. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ ACPM/AGS? APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(24):e285–e350. doi: 10.1016/j.jacc.2018.11.003. 
15. Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. 2016; 388(10059):2532–2561. doi: 10.1016/S0140-6736(16)313575.
16. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015; 372: 2387–2397. doi: 10.1056/NEJMoa1410489. 
17. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular Disease. N Engl J Med. 2017; 376: 1713–1722. doi: 10.1056/NEJMoa1615664.
18. Schwartz GG, Steg PG, Szarek M, et al. ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018; 379: 2097–2107. doi: 10.1056/NEJMoa1801174. 
19. Cholesterol Treatment Trialists’ (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. 2012;380: 581–590. doi:10.1016/S0140-6736(12)60367-5.
20. Jarcho JA, Keaney JF., Jr Proof that lower is better: LDL cholesterol and IMPROVE-IT. N Engl J Med. 2015; 372: 2448–2450. doi: 10.1056/NEJMe1507041. 
21. Navarese EP, Robinson JG, Kowalewski M, et al. Association between baseline LDL-C level and total and cardiovascular mortality after LDL-C lowering: a systematic review and meta-analysis [published correction appears in JAMA. 2018 Oct 2;320(13):1387] 2018; 319(15):1566–1579. doi: 10.1001/jama.2018.2525. 
22. Lemus HN, Mendivil CO. Adenosine triphosphate citrate lyase: emerging target in the treatment of dyslipidemia. J ClinLipidol. 2015; 9 (3):384–389. doi: 10.1016/j.jacl.2015.01.002. 
23. Ruscica M, Banach M, Sahebkar A, Corsini A, Sirtori CR. ETC-1002 (Bempedoic acid) for the management of hyperlipidemia: from preclinical studies to phase 3 trials. Expert Opin Pharmacother. 2019; 20 (7):791–803. doi: 10.1080/14656566.2019.1583209. 
24. Pathy K. Bempedoic acid a small molecule drug process and synthesis, innovation and/or advantages, development status and/or regulatory status. Sur Cas Stud Op Acc J. 2019; 3(1):222–227. doi: 10.32474/scsoaj.2019.03.000154.
25. Samsoondar JP, Burke AC, Sutherland BG, et al. Prevention of diet-induced metabolic dysregulation, inflammation, and atherosclerosis in ldlr−/− mice by treatment with the atp-citrate lyase inhibitor bempedoic acid. Arterioscler Thromb Vasc Biol. 2017;37: 647–656. doi: 10.1161/ATVBAHA.116.308963. 

Harichandana Punukula