Role of Bempedoic Acid in Dyslipidemia Management.
Journal
Journal of cardiovascular pharmacology
ISSN: 1533-4023
Titre abrégé: J Cardiovasc Pharmacol
Pays: United States
ID NLM: 7902492
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
pubmed:
1
8
2020
medline:
7
7
2021
entrez:
1
8
2020
Statut:
ppublish
Résumé
Statins remain the preferred agent to reduce low-density lipoprotein cholesterol (LDL-C) and lower atherosclerotic cardiovascular disease (ASCVD) risk. Additional nonstatin agents are recommended to further lower LDL-C among patients at high-risk of ASCVD or those with heterozygous familial hypercholesterolemia, despite statin therapy. Patients unable to tolerate recommended doses of statin therapy due to adverse effects, including statin-associated muscle symptoms, may also require additional nonstatin agents to lower LDL-C and ASCVD risk. Bempedoic acid is a first-in-class, once-daily oral agent, recently approved as monotherapy and in combination with ezetimibe, as an adjunct to maximally tolerated statin therapy in patients with ASCVD or heterozygous familial hypercholesterolemia who require additional LDL-C lowering. Its novel mechanism is reported to avoid adverse muscle symptoms associated with statins. The effectiveness and safety of bempedoic acid and bempedoic acid/ezetimibe combination have been reported in multiple phase 2 and 3 trials. In this review, we report the lipid-lowering effects associated with bempedoic acid, and the safety profile from multiple clinical trials. Based on available data, bempedoic acid significantly lowers LDL-C and other atherogenic lipoprotein measures, and high-sensitivity C-reactive protein when added to background lipid-lowering therapy in patients with and without statin intolerance. Overall safety of bempedoic acid seems to be comparable to placebo, except for increased serum uric acid and tendon rupture. Ongoing clinical trials assessing the long-term safety and cardiovascular outcomes will provide additional insight into the role of bempedoic acid as an adjunct lipid-lowering medication.
Identifiants
pubmed: 32732494
doi: 10.1097/FJC.0000000000000887
pii: 00005344-202010000-00004
doi:
Substances chimiques
Anticholesteremic Agents
0
Biomarkers
0
Cholesterol, LDL
0
Dicarboxylic Acids
0
Fatty Acids
0
8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
1EJ6Z6Q368
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
376-388Commentaires et corrections
Type : CommentIn
Références
Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/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. Circulation. 2019;139:e1082-e1143.
Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med. 1999;340:115–126.
Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–1681.
Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495–1504.
Thompson PD, Panza G, Zaleski A, et al. Statin-associated side effects. J Am Coll Cardiol. 2016;67:2395–2410.
Stroes ES, Thompson PD, Corsini A, et al. Statin-associated muscle symptoms: impact on statin therapy-European atherosclerosis society consensus panel statement on assessment, aetiology and management. Eur Heart J. 2015;36:1012–1022.
Nexletol [package insert]. Ann Arbor, MI: Esperion Therapeutics, INC; 2020.
Nexlizet [package insert]. Ann Arbor, MI: Esperion Therapeutics, INC; 2020.
Penson P, McGowan M, Banach M. Evaluating bempedoic acid for the treatment of hyperlipidaemia. Expert Opin Investig Drugs. 2017;26:251–259.
Pinkosky SL, Filippov S, Srivastava RAK, 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;54:134–151.
A Multiple Ascending Dose Study of ETC-1002 in Subjects with Mild Dyslipidemia—Full Text View—ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/study/NCT01105598. Accessed May 25, 2020.
United States Securities and Exchange Commission. Esperion Therapeutics Inc. Form 10-K—Annual Report. 2014. Available at: https://www.sec.gov/Archives/edgar/data/1434868/000104746915001908/a2223469z10-k.htm#bg19801a_main_toc. Accessed May 18, 2020.
A Multiple Ascending Dose Study of ETC-1002 in Healthy Subjects—Full Text View—ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT01485146. Accessed May 25, 2020.
Lalwani ND, Hanselman JC, MacDougall DE, et al. Complementary low-density lipoprotein-cholesterol lowering and pharmacokinetics of adding bempedoic acid (ETC-1002) to high-dose atorvastatin background therapy in hypercholesterolemic patients: a randomized placebo-controlled trial. J Clin Lipidol. 2019;13:568–579.
Ballantyne CM, McKenney JM, MacDougall DE, et al. Effect of ETC-1002 on serum low-density lipoprotein cholesterol in hypercholesterolemic patients receiving statin therapy. Am J Cardiol. 2016;117:1928–1933.
McKenney J, MacDougall D, Sterling LR, et al. Lipid lowering with bempedoic acid added to proprotein convertase subtilisin/kexin type 9 inhibitor therapy: a randomized controlled trial. J Clin Lipidol. 2019;13:e55–e56.
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;8:1–13.
Goldberg AC, Leiter LA, Stroes ESG, 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;322:1780–1788.
Ray KK, Bays HE, Catapano AL, et al. Safety and efficacy of bempedoic acid to reduce LDL cholesterol. N Engl J Med. 2019;380:1022–1032.
Thompson PD, MacDougall DE, Newton RS, et al. 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;10:556–567.
Ballantyne CM, Laufs U, Ray KK, et al. Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy. Eur J Prev Cardiol. 2020;27:593–603.
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.
Center for Drug Evaluation and Research Application Number: 211616Orig1s000 Integrated Review Executive Summary Interdisciplinary Assessment Appendices. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211616Orig1s000IntegratedR.pdf. Accessed May 25, 2020.
Cicero AFG, Pontremoli R, Fogacci F, et al. Effect of bempedoic acid on serum uric acid and related outcomes: a systematic review and meta-analysis of the available phase 2 and phase 3 clinical studies. Drug Saf. 2020;43:727–736.
Assessment of the Long-Term Safety and Efficacy of Bempedoic Acid (CLEAR Harmony OLE)—Full Text View—ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT03067441. Accessed May 25, 2020.
Evaluation of Major Cardiovascular Events in Patients With, or at High Risk for, Cardiovascular Disease Who are Statin Intolerant Treated With Bempedoic Acid (ETC-1002) or Placebo—Full Text View—ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT02993406?term=02993406&draw=2&rank=1. Accessed May 25, 2020.
Farnier M, Guyton JR, Jensen E, et al. Effects of ezetimibe, simvastatin and ezetimibe/simvastatin on correlations between apolipoprotein B, LDL cholesterol and non-HDL cholesterol in patients with primary hypercholesterolemia. Atherosclerosis. 2013;229:415–422.
Bonnet J, McPherson R, Tedgui A, et al. Comparative effects of 10-mg versus 80-mg Atorvastatin on high-sensitivity C-reactive protein in patients with stable coronary artery disease: results of the CAP (Comparative Atorvastatin Pleiotropic effects) study. Clin Ther. 2008;30:2298–2313.
Bohula EA, Giugliano RP, Cannon CP, et al. Achievement of dual low-density lipoprotein cholesterol and high-sensitivity C-reactive protein targets more frequent with the addition of ezetimibe to simvastatin and associated with better outcomes in IMPROVE-IT. Circulation. 2015;132:1224–1233.
Cao YX, Li S, Liu HH, et al. Impact of PCSK9 monoclonal antibodies on circulating hs-CRP levels: a systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2018;8:e022348.
Ridker PM, Danielson E, Fonseca FAH, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–2207.
Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119–1131.
Ridker PM, Everett BM, Pradhan A, et al. Low-dose methotrexate for the prevention of atherosclerotic events. N Engl J Med. 2018;380:752–762.
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.
Ference BA, Ray KK, Catapano AL, et al. Mendelian randomization study of ACLY and cardiovascular disease. N Engl J Med. 2019;380:1033–1042.