Bempedoic acid – a new drug to lower LDL-cholesterol level
Authors:
Vladimír Soška 1,2; Ondřej Kyselák 1,3
Authors place of work:
Oddělení klinické biochemie FN U sv. Anny v Brně
1; II. interní klinika LF MU a FN U sv. Anny v Brně
2; Katedra laboratorních metod LF MU, Brno
3
Published in the journal:
AtheroRev 2022; 7(3): 147-151
Category:
Reviews
Summary
Lowering LDL-cholesterol is a key step in reducing the risk of atherosclerotic cardiovascular diseases. Statins are the mainstay of therapy, to which ezetimibe may be added in combination, and PCSK9 inhibitors may also be used in some patients meeting the indication criteria. In the near future, the portfolio of hypolipidemics may be expanded to include bempedoic acid. Bempedoic acid suppresses cholesterol synthesis by inhibiting the enzymatic activity of ATP-citrate lyase, which catalyses the initial step of cholesterol synthesis. Phase III clinical trials have demonstrated the safety of this drug and its efficacy in lowering LDL-cholesterol in statin-intolerant patients, patients on maximally tolerated statin doses, as well as its very good efficacy when combined with ezetimibe. The effect of bempedoic acid therapy on the frequency of atherosclerotic cardiovascular events is to be demonstrated in the CLEAR Outcome clinical trial.
Keywords:
Metabolism – Cholesterol – bempedoic acid – LDL-cholesterol – CLEAR Outcome clinical trial
Zdroje
1. Ference BA, Ginsberg HN, Graham I et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2017; 38(32): 2459–2472. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehx144>.
2. Boren J, Chapman MJ, Krauss RM et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2020; 41(24): 2313–2330.Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehz962>.
3. Piepoli MF, Hoes AW, Agewall S et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis 2016; 252: 207–274. Dostupné z DOI: . <http://dx.doi.org/10.1016/j.atherosclerosis.2016.05.037>.
4. Visseren FLJ, Mach F, Smulders YM et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2021; 42(34): 3227–3337. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehab484>
5. Pinkosky SL, Filippov S, Srivastava RA 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; 54(1): 134–151.Dostupné z DOI: <http://dx.doi.org/10.1194/jlr.M030528>.
6. Cicero AF, Fogacci F, Cincione I. Evaluating pharmacokinetics of bempedoic acid in the treatment of hypercholesterolemia. Expert Opin Drug Metab Toxicol 2021; 17(9): 1031–1038. Dostupné z DOI: <http://dx.doi.org/10.1080/17425255.2021.1951222>.
7. Pinkosky SL, Newton RS, Day EA et al. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun 2016; 7: 13457. Dostupné z DOI: <http://dx.doi.org/10.1038/ncomms13457>.
8. Bilen O, Ballantyne CM. Bempedoic Acid (ETC-1002): an Investigational Inhibitor of ATP Citrate Lyase. Curr Atheroscler Rep 2016; 18(10): 61. Dostupné z DOI: <http://dx.doi.org/10.1007/s11883–016–0611–4>.
9. Ballantyne CM, Bays H, Catapano AL et al. Role of Bempedoic Acid in Clinical Practice. Cardiovasc Drugs Ther 2021; 35(4): 853–864. Dostupné z DOI: <http://dx.doi.org/10.1007/s10557–021–07147–5>.
10. Pirillo A, Catapano AL. New insights into the role of bempedoic acid and ezetimibe in the treatment of hypercholesterolemia. Curr Opin Endocrinol Diabetes Obes 2022; 29(2): 161–166. Dostupné z DOI: <http://dx.doi.org/10.1097/MED.0000000000000706>.
11. Jadhav SB, Crass RL, Chapel S et al. Pharmacodynamic effect of bempedoic acid and statin combinations: predictions from a dose-response model. Eur Heart J Cardiovasc Pharmacother 2022; 8(6): 578–586. Dostupné z DOI: <http://dx.doi.org/10.1093/ehjcvp/pvab064>.
12. Ballantyne CM, Banach M, Mancini GBJ et al. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study. Atherosclerosis 2018; 277: 195–203. Dostupné z DOI: <http://dx.doi.org/10.1016/j.atherosclerosis.2018.06.002>.
13. Laufs U, Banach M, Mancini GBJ et al. Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance. J Am Heart Assoc 2019; 8(7): e011662. Dostupné z DOI: <http://dx.doi.org/10.1161/JAHA.118.011662>.
14. Leiter LA, Banach M, Catapano AL et al. Bempedoic acid in patients with type 2 diabetes mellitus, prediabetes, and normoglycaemia: A post hoc analysis of efficacy and glycaemic control using pooled data from phase 3 clinical trials. Diabetes Obes Metab 2022; 24(5): 868–880. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.14645>.
15. Bays HE, Baum SJ, Brinton EA et al. Effect of bempedoic acid plus ezetimibe fixed-dose combination vs ezetimibe or placebo on low-density lipoprotein cholesterol in patients with type 2 diabetes and hypercholesterolemia not treated with statins. Am J Prev Cardiol 2021; 8: 100278. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ajpc.2021.100278>.
16. Masson W, Lobo M, Lavalle-Cobo A et al. Effect of bempedoic acid on new onset or worsening diabetes: A meta-analysis. Diabetes Res Clin Pract 2020; 168: 108369. Dostupné z DOI: <http://dx.doi.org/10.1016/j.diabres.2020.108369>.
17. Sato M, Mamada H, Anzai N et al. Renal secretion of uric acid by organic anion transporter 2 (OAT2/SLC22A7) in human. Biol Pharm Bull 2010; 33(3): 498–503. Dostupné z DOI: <http://dx.doi.org/10.1248/bpb.33.498>.
18. Bardolia C, Amin NS, Turgeon J. Emerging Non-statin Treatment Options for Lowering Low-Density Lipoprotein Cholesterol. Front Cardiovasc Med 2021; 8: 789931. Dostupné z DOI: <http://dx.doi.org/10.3389/fcvm.2021.789931>.
19. Ray KK, Bays HE, Catapano AL et al. Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. N Engl J Med 2019; 380(11): 1022–1032. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1803917>.
20. Goldberg AC, Leiter LA, Stroes ES et al. Effect of Bempedoic Acid vs Placebo Added to Maximally Tolerated Statins on Low-Density Lipoprotein Cholesterol in Patients at High Risk for Cardiovascular Disease: The CLEAR Wisdom Randomized Clinical Trial. JAMA 2019; 322(18): 1780–1788. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2019.16585>.
21. Banach M, Duell PB, Gotto AM, Jr et al. Association of Bempedoic Acid Administration With Atherogenic Lipid Levels in Phase 3 Randomized Clinical Trials of Patients With Hypercholesterolemia. JAMA Cardiol 2020; 5(10): 1124–1135. Dostupné z DOI: <http://dx.doi.org/10.1001/jamacardio.2020.2314>.
22. Dai L, Zuo Y, You Q et al. Efficacy and safety of bempedoic acid in patients with hypercholesterolemia: A systematic review and meta-analysis of randomized controlled trials. Eur J Prev Cardiol 2021; 28(8): 825–833. Dostupné z DOI: <http://dx.doi.org/10.1177/2047487320930585>.
23. Bays HE, Banach M, Catapano AL et al. Bempedoic acid safety analysis: Pooled data from four phase 3 clinical trials. J Clin Lipidol 2020; 14(5): 649–659 e646. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacl.2020.08.009>.
24. Masson W, Lobo M, Lavalle-Cobo A et al. Effect of Bempedoic Acid on atherogenic lipids and inflammation: A meta-analysis. Clin Investig Arterioscler 2021; 33(3): 117–126. Dostupné z DOI: <http://dx.doi.org/10.1016/j.arteri.2020.09.002>.
25. Nicholls S, Lincoff AM, Bays HE et al. 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; 235: 104–112.Dostupné z DOI: <http://dx.doi.org/10.1016/j.ahj.2020.10.060>.
26. Nilmedo. SPC. SÚKL. Dostupné z WWW. <https://www.sukl.cz/modules/medication/detail.php?code=0238919&tab=texts>.
27. Blaum C, Brunner FJ, Gossling A et al. Target Populations and Treatment Cost for Bempedoic Acid and PCSK9 Inhibitors: A Simulation Study in a Contemporary CAD Cohort. Clin Ther 2021; 43(9): 1583–1600. Dostupné z DOI: <http://dx.doi.org/10.1016/j.clinthera.2021.07.019>.
28. Lin Y, Parco C, Karathanos A et al. Clinical efficacy and safety outcomes of bempedoic acid for LDL-C lowering therapy in patients at high cardiovascular risk: a systematic review and meta-analysis. BMJ Open 2022; 12(2): e048893. Dostupné z DOI: <http://dx.doi.org/10.1136/bmjopen-2021–048893>.
Štítky
Angiology Diabetology Internal medicine Cardiology General practitioner for adultsČlánok vyšiel v časopise
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