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bempedoic acid (Nexletol)

Indications: - hypertension - dyslipidemia (hyperlipidemia, hypercholesterolemia) - may lower LDL cholesterol when added to statin [2,3] - treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease [4] - high-risk primary prevention patients [7] - used in combination with ezetimibe 10 mg - type 2 diabetes - reduces LDL cholesterol, serum C-reactive protein & cardiovascular risk [8] Dosage: - 180 mg PO QD Pharmarmacokinetics: - prodrug Adverse effects: - slight increase in tendon rupture - hyperuricemia - benign prostatic hyperplasia - atrial fibrillation [5] - does not increase risk of new-onset diabetes or worsening or HbA1c [8] Mechanism of action: - inhibits ATP citrate lyase enzyme, involved in cholesterol metabolism upstream to HMG-CoA reductase, the target of statins [2] - lowers LDL cholesterol by suppressing cholesterol synthesis & upregulating LDL receptors - decreases LDL cholesterol by 15% over statin alone & by 38% when used in combination with ezetimibe [5]

General

alcohol carboxylate enzyme inhibitor metabolic agent (metabolic modifier)

Database Correlations

PUBCHEM cid=10472693

References

  1. PubChem: 10472693
  2. 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 https://www.nejm.org/doi/full/10.1056/NEJMoa1803917
  3. Goldberg AC 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 PMID: 31714986 https://jamanetwork.com/journals/jama/fullarticle/2754792
  4. Wendling P Patrice Wendling. New Lipid-Lowering Drug Earns FDA Approval. Medscape - Feb 21, 2020. https://www.medscape.com/viewarticle/925580
  5. Lloyd-Jones DM, Morris PB, Ballantyne CM et al 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2022 Oct, 80 (14) 1366-1418 PMID: 36031461 https://www.jacc.org/doi/10.1016/j.jacc.2022.07.006
  6. Nissen SE et al Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. N Engl J Med. 2023. March 4 PMID: 36876740 https://www.nejm.org/doi/10.1056/NEJMoa2215024
  7. Nissen SE, Menon V, Nicholls SJ et al Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin- Intolerant Patients. JAMA. Published online June 24, 2023 PMID: 37354546 https://jamanetwork.com/journals/jama/fullarticle/2806646
  8. Ray KK, Nicholls SJ, Li N, et al. 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 PMID: 38061370 Free article https://www.thelancet.com/journals/landia/article/PIIS2213-8587(23)00316-9/fulltext