Harold E Bays1, Maciej Banach2, Alberico L Catapano3, P Barton Duell4, Antonio M Gotto5, Ulrich Laufs6, Lawrence A Leiter7, G B John Mancini8, Kausik K Ray9, LeAnne T Bloedon10, William J Sasiela10, Zhan Ye10, Christie M Ballantyne11. 1. Louisville Metabolic and Atherosclerosis Research Center, Louisville, Kentucky, USA. Electronic address: hbaysmd@outlook.com. 2. Department of Hypertension, Medical University of Łódź, Łódź, Poland. 3. Department of Pharmacological and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milan, Italy. 4. Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA. 5. Houston Methodist Research Institute, Houston, Texas, USA; Weill Cornell Medicine, New York, New York, USA. 6. Klinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, Leipzig, Germany. 7. Division of Endocrinology & Metabolism, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. 8. Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada. 9. Department of Primary Care and Public Health, Imperial Centre for Cardiovascular Disease Prevention, Imperial College London, London, UK. 10. Esperion Therapeutics, Inc., Ann Arbor, Michigan, USA. 11. Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Abstract
BACKGROUND: An ongoing need exists for safe and effective lipid-lowering therapies (LLTs) for patients unable to achieve desired lipid levels with current treatment options. OBJECTIVE: The objective of this study was to describe the safety profile of bempedoic acid, an oral, first-in-class, adenosine triphosphate (ATP)-citrate lyase inhibitor that significantly reduces low-density lipoprotein cholesterol (LDL-C) levels by 17.4%-28.5% vs placebo. METHODS: This was a pooled analysis of four phase 3, randomized (2:1), double-blind, placebo-controlled studies in patients with hypercholesterolemia who required additional LDL-C lowering, despite stable maximally-tolerated LLT. Patients received 180 mg of bempedoic acid (n = 2424) or placebo (n = 1197) once daily for 12 to 52 weeks. Assessments included treatment-emergent adverse events (TEAEs) and clinical laboratory tests. RESULTS: Of 3621 patients (the median drug exposure: 363 days), exposure-adjusted TEAE rates were 87.1/100 and 82.9/100 person-years (PY) forbempedoic acid and placebo, respectively. No single TEAE influenced the difference in rates. TEAEs leading to discontinuation occurred at rates of 13.4/100 and 8.9/100 PY for bempedoic acid vs placebo, with the most common cause being myalgia, which occurred less frequently with bempedoic acid vs placebo (1.5/100 vs 2.0/100 PY). Rates of myalgia and muscle weakness were comparable vs placebo. Bempedoic acid was associated with mild increases in blood urea nitrogen, creatinine, and uric acid and decreases in hemoglobin. These laboratory abnormalities were apparent by week 4, stable over time, and reversible after treatment cessation. Gout incidence was 1.6/100 vs 0.5/100 PY in the bempedoic acid vs placebo groups. New-onset diabetes/hyperglycemia occurred less frequently with bempedoic acid vs placebo (4.7/100 vs 6.4/100 PY). The safety profile was consistent across subgroups. CONCLUSIONS:Bempedoic acid is generally safe and well tolerated among patients with hypercholesterolemia who require additional LLT.
RCT Entities:
BACKGROUND: An ongoing need exists for safe and effective lipid-lowering therapies (LLTs) for patients unable to achieve desired lipid levels with current treatment options. OBJECTIVE: The objective of this study was to describe the safety profile of bempedoic acid, an oral, first-in-class, adenosine triphosphate (ATP)-citrate lyase inhibitor that significantly reduces low-density lipoprotein cholesterol (LDL-C) levels by 17.4%-28.5% vs placebo. METHODS: This was a pooled analysis of four phase 3, randomized (2:1), double-blind, placebo-controlled studies in patients with hypercholesterolemia who required additional LDL-C lowering, despite stable maximally-tolerated LLT. Patients received 180 mg of bempedoic acid (n = 2424) or placebo (n = 1197) once daily for 12 to 52 weeks. Assessments included treatment-emergent adverse events (TEAEs) and clinical laboratory tests. RESULTS: Of 3621 patients (the median drug exposure: 363 days), exposure-adjusted TEAE rates were 87.1/100 and 82.9/100 person-years (PY) for bempedoic acid and placebo, respectively. No single TEAE influenced the difference in rates. TEAEs leading to discontinuation occurred at rates of 13.4/100 and 8.9/100 PY for bempedoic acid vs placebo, with the most common cause being myalgia, which occurred less frequently with bempedoic acid vs placebo (1.5/100 vs 2.0/100 PY). Rates of myalgia and muscle weakness were comparable vs placebo. Bempedoic acid was associated with mild increases in blood ureanitrogen, creatinine, and uric acid and decreases in hemoglobin. These laboratory abnormalities were apparent by week 4, stable over time, and reversible after treatment cessation. Gout incidence was 1.6/100 vs 0.5/100 PY in the bempedoic acid vs placebo groups. New-onset diabetes/hyperglycemia occurred less frequently with bempedoic acid vs placebo (4.7/100 vs 6.4/100 PY). The safety profile was consistent across subgroups. CONCLUSIONS:Bempedoic acid is generally safe and well tolerated among patients with hypercholesterolemia who require additional LLT.
Authors: Benny M Amore; Clay T Cramer; Diane E MacDougall; William J Sasiela; Maurice G Emery Journal: Clin Transl Sci Date: 2021-08-31 Impact factor: 4.689
Authors: Harold E Bays; Seth J Baum; Eliot A Brinton; Jorge Plutzky; Jeffrey C Hanselman; Rujun Teng; Christie M Ballantyne Journal: Am J Prev Cardiol Date: 2021-10-04
Authors: Christie M Ballantyne; Harold Bays; Alberico L Catapano; Anne Goldberg; Kausik K Ray; Joseph J Saseen Journal: Cardiovasc Drugs Ther Date: 2021-04-05 Impact factor: 3.727