Volume : 11, Issue : 02, February – 2024
Title:
A REVIEW ARTICLE ON BEMPEDOIC ACID – ANTI HYPERLIPIDEMIC DRUG
Authors :
R . Jona Methusala , S. Nikhath Kousar
Abstract :
Bempedoic acid is a prodrug that, once activated, decreases LDL-C levels by the inhibition of adenosine triphosphate citrate lyase in the liver. Five clinical trials have demonstrated the safety and efficacy of bempedoic acid and the bempedoic acid/ezetimibe combination in lowering LDL-C in patients with atherosclerotic CVD and heterozygous familial hypercholesterolemia and also in high-risk primary prevention, and statin-intolerant patients. Bempedoic acid has been demonstrated to lower LDL-C levels by 15-25% in clinical trials and up to 38% when combined with ezetimibe. In 2020, the FDA approved bempedoic acid. Furthermore, the combination of bempedoic acid with ezetimibe is FDA approved for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic CVD who require additional LDL-C lowering after maximally tolerated statin therapy. The ongoing CLEAR OUTCOMES trial aims to evaluate whether bempedoic acid can reduce cardiovascular events in patients with statin intolerance and results will be available in the next 3 years. This outcomes trial will be pivotal for determining the role of bempedoic acid in the non-statin lipid-lowering armamentarium.
Keywords: bempedoic acid; cardiovascular events; dyslipidemia; hypercholesterolemia; low- density lipoprotein-cholesterol.
Cite This Article:
Please cite this article in press Nikhath Kousar et al., A Review Article On Bempedoic Acid – Anti Hyperlipidemic Drug, Indo Am. J. P. Sci, 2024; 11 (02).
Number of Downloads : 10
References:
1. Khera AV, Hegele RA. What is familial hypercholesterolemia, and why does it matter? Circulation. 2020;141(22):1760–1763. doi:10.1161/CIRCULATIONAHA.120.046961
2. Michos ED, McEvoy JW, Blumenthal RS. Lipid management for the prevention of atherosclerotic cardiovascular disease. N Engl J Med. 2019;381(16):1557–1567. doi:10.1056/NEJMra1806939
3. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–2397. doi:10.1056/NEJMoa1410489
4. Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1489–1499. doi:10.1056/NEJMoa1501031
5. S.M. Grundyetal.2018AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/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
6. J Am Coll Cardiol (2019) S.M. Boekholdt et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta analysis of statin trials
7. J Am Coll Cardiol (2014 )C. Ballantyne et al. Efficacy and safety of Bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: a randomized, placebo- controlled study Atherosclerosis
8. C. Gagné et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia
9. Am J Cardiol (2002)P. Thompson et al. Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance
10. J Clin Lipidol (2016)A.A.A. Asbeutah et al. A meta-analysis of cardiovascular outcomes in patients with hypercholesterolemia treated with Bempedoic acid.
11. Am J Cardiol (2020) B. Sjouke et al. Homozygous autosomal dominant hyper cholesterolaemia in The Netherlands: prevalence, genotype-phenotype relationship, and clinical outcome
12. Amore BM, Cramer CT, MacDougall DE, Sasiela WJ, and Emery MG (2021a) Absence of effect of steady state Bempedoic acid on cardiac repolarization: Results of a thorough QT/QTc study in healthy volunteers. Clin Transl Sci 14:2487–2496.OpenUrlGoogle Scholar
13. Amore BM, Sasiela WJ, and Emery MG (2021b) The effects of impaired hepatic function on pharmacokinetics of Bempedoic acid,
14,A first-in-class adenosine triphosphate (ATP) citrate lyase inhibitor, evaluated in an open- label, single-dose, parallel-group study (Abstract PIII-030). Clin Pharmacol Ther 109:S53.
15. Amore BM, Sasiela WJ, Ries DK, Tresh P, and Emery MG (2022) Pharmacokinetics of Bempedoic acid in patients with renal impairment. Clin Transl Sci 15:789–798.OpenUrlGoogle Scholar
16. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J et al. (2010) Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376:1670–1681.OpenUrlCrossRefPubMedGoogle Scholar
17. Ballantyne CM, Banach M, Mancini GBJ, Lepor NE, Hanselman JC, Zhao X, and Leiter LA (2018) Efficacy and safety of Bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study. Atherosclerosis 277:195–203.OpenUrlCrossRefPubMedGoogle Scholar
18. Bays HE, Banach M, Catapano AL, Duell PB, Gotto Jr AM, Laufs U, Leiter LA, Mancini GBJ, Ray KK, Bloedon LT, et al. (2020) Bempedoic acid safety analysis: Pooled data from four phase 3 clinical trials. J Clin Lipidol 1
19. Kilkenny C, Parsons N, Kadyszewski E, Festing MFW, Cuthill IC, et al. Survey of the Quality of Experimental Design, Statistical Analysis and Reporting of Research Using Animals. PLoS ONE. 2009;4(11):e7824. doi: 10.1371/journal.pone.0007824. 19.Landis SC, Amara SG.
20. Asadullah K, et al. A call for transparent reporting to optimize the predictive value of preclinical research. Nature. 2012;490(7419):187–191.
21. Little RJA, Rubin DB. Statistical analysis with missing data. 2. New York: Wiley & Sons; 2002.
22. Piddlesden SJ, Jiang S, Levin JL, et al. Soluble complement receptor 1 (sCR1) protects against experimental autoimmune myasthenia gravis. J Neuroimmunol. 1996;71:173177. [Pub Med ] [Google Scholor ]
23. Soltys J, Kusner L, Young A, Richmonds C, Hatala D, Gong B, Shanmugavel V, Kaminski
H. Novel Complement Inhibitor Limits Severity of Experimentally Myasthenia Gravis. Ann Neurol. 2009;65(1):6775.
24. Warner DS, James ML, Laskowitz DT, Wijdicks EF. Translational research in acute central nervous system injury: lessons learned and the future. JAMA Neurol. (71) 2014 Oct 1;(10):1311–8. [Pub med ] [ Google Scholor ]
25. PinkoskySL, FilippovS, SrivastavaRA, et al. AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism. J Lipid Res. 2013 34–151. doi:10.1194/jlr.M03052823118444
26. JeongHW, HsuKC, LeeJW, et al. Berberine suppresses proinflammatory responses through AMPK activation in macrophages. Am J Physiol Endocrinol Metab. 2009; E955–964. doi:10.1152/ajpendo.90599.200819208854
27. SamsoondarJP, BurkeAC, Sutherl and 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. 2017:647–656. doi:10.1161/ATVBAHA.116.30896328153881
28. A Multiple Ascending Dose Study of ETC-1002 in healthy subjects; 2019. Available from Accessed 79, 2019.