Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance
Background Inability to tolerate statins because of muscle symptoms contributes to uncontrolled cholesterol levels and insufficient cardiovascular risk reduction. Bempedoic acid, a prodrug that is activated by a hepatic enzyme not present in skeletal muscle, inhibits ATP‐citrate lyase, an enzyme ups...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-04-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.118.011662 |
| _version_ | 1811275117415628800 |
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| author | Ulrich Laufs Maciej Banach G. B. John Mancini Daniel Gaudet LeAnne T. Bloedon Lulu Ren Sterling Stephanie Kelly Erik S. G. Stroes |
| author_facet | Ulrich Laufs Maciej Banach G. B. John Mancini Daniel Gaudet LeAnne T. Bloedon Lulu Ren Sterling Stephanie Kelly Erik S. G. Stroes |
| author_sort | Ulrich Laufs |
| collection | DOAJ |
| description | Background Inability to tolerate statins because of muscle symptoms contributes to uncontrolled cholesterol levels and insufficient cardiovascular risk reduction. Bempedoic acid, a prodrug that is activated by a hepatic enzyme not present in skeletal muscle, inhibits ATP‐citrate lyase, an enzyme upstream of β‐hydroxy β‐methylglutaryl‐coenzyme A reductase in the cholesterol biosynthesis pathway. Methods and Results The phase 3, double‐blind, placebo‐controlled CLEAR (Cholesterol Lowering via Bempedoic acid, an ACL‐Inhibiting Regimen) Serenity study randomized 345 patients with hypercholesterolemia and a history of intolerance to at least 2 statins (1 at the lowest available dose) 2:1 to bempedoic acid 180 mg or placebo once daily for 24 weeks. The primary end point was mean percent change from baseline to week 12 in low‐density lipoprotein cholesterol. The mean age was 65.2 years, mean baseline low‐density lipoprotein cholesterol was 157.6 mg/dL, and 93% of patients reported a history of statin‐associated muscle symptoms. Bempedoic acid treatment significantly reduced low‐density lipoprotein cholesterol from baseline to week 12 (placebo‐corrected difference, −21.4% [95% CI, −25.1% to −17.7%]; P<0.001). Significant reductions with bempedoic acid versus placebo were also observed in non–high‐density lipoprotein cholesterol (−17.9%), total cholesterol (−14.8%), apolipoprotein B (−15.0%), and high‐sensitivity C‐reactive protein (−24.3%; P<0.001 for all comparisons). Bempedoic acid was safe and well tolerated. The most common muscle‐related adverse event, myalgia, occurred in 4.7% and 7.2% of patients who received bempedoic acid or placebo, respectively. Conclusions Bempedoic acid offers a safe and effective oral therapeutic option for lipid lowering in patients who cannot tolerate statins. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02988115. |
| first_indexed | 2024-04-12T23:32:22Z |
| format | Article |
| id | doaj.art-2f1c02e8e5274f348c35a1f0d855216e |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-12T23:32:22Z |
| publishDate | 2019-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-2f1c02e8e5274f348c35a1f0d855216e2022-12-22T03:12:14ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802019-04-018710.1161/JAHA.118.011662Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin IntoleranceUlrich Laufs0Maciej Banach1G. B. John Mancini2Daniel Gaudet3LeAnne T. Bloedon4Lulu Ren Sterling5Stephanie Kelly6Erik S. G. Stroes7Klinik und Poliklinik für Kardiologie Universitätsklinikum Leipzig Leipzig GermanyDepartment of Hypertension Medical University of Lodz PolandDivision of Cardiology University of British Columbia Vancouver British Columbia CanadaLipidology Unit, Community Genomic Medicine Centre and ECOGENE‐21 Department of Medicine Université de Montréal Saguenay Quebec CanadaEsperion Therapeutics, Inc. Ann Arbor MIEsperion Therapeutics, Inc. Ann Arbor MIEsperion Therapeutics, Inc. Ann Arbor MIDepartment of Vascular Medicine Academic Medical Center of Amsterdam NetherlandsBackground Inability to tolerate statins because of muscle symptoms contributes to uncontrolled cholesterol levels and insufficient cardiovascular risk reduction. Bempedoic acid, a prodrug that is activated by a hepatic enzyme not present in skeletal muscle, inhibits ATP‐citrate lyase, an enzyme upstream of β‐hydroxy β‐methylglutaryl‐coenzyme A reductase in the cholesterol biosynthesis pathway. Methods and Results The phase 3, double‐blind, placebo‐controlled CLEAR (Cholesterol Lowering via Bempedoic acid, an ACL‐Inhibiting Regimen) Serenity study randomized 345 patients with hypercholesterolemia and a history of intolerance to at least 2 statins (1 at the lowest available dose) 2:1 to bempedoic acid 180 mg or placebo once daily for 24 weeks. The primary end point was mean percent change from baseline to week 12 in low‐density lipoprotein cholesterol. The mean age was 65.2 years, mean baseline low‐density lipoprotein cholesterol was 157.6 mg/dL, and 93% of patients reported a history of statin‐associated muscle symptoms. Bempedoic acid treatment significantly reduced low‐density lipoprotein cholesterol from baseline to week 12 (placebo‐corrected difference, −21.4% [95% CI, −25.1% to −17.7%]; P<0.001). Significant reductions with bempedoic acid versus placebo were also observed in non–high‐density lipoprotein cholesterol (−17.9%), total cholesterol (−14.8%), apolipoprotein B (−15.0%), and high‐sensitivity C‐reactive protein (−24.3%; P<0.001 for all comparisons). Bempedoic acid was safe and well tolerated. The most common muscle‐related adverse event, myalgia, occurred in 4.7% and 7.2% of patients who received bempedoic acid or placebo, respectively. Conclusions Bempedoic acid offers a safe and effective oral therapeutic option for lipid lowering in patients who cannot tolerate statins. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02988115.https://www.ahajournals.org/doi/10.1161/JAHA.118.011662hypercholesterolemialipidslow‐density lipoprotein cholesterolmusclestatin |
| spellingShingle | Ulrich Laufs Maciej Banach G. B. John Mancini Daniel Gaudet LeAnne T. Bloedon Lulu Ren Sterling Stephanie Kelly Erik S. G. Stroes Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease hypercholesterolemia lipids low‐density lipoprotein cholesterol muscle statin |
| title | Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance |
| title_full | Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance |
| title_fullStr | Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance |
| title_full_unstemmed | Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance |
| title_short | Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance |
| title_sort | efficacy and safety of bempedoic acid in patients with hypercholesterolemia and statin intolerance |
| topic | hypercholesterolemia lipids low‐density lipoprotein cholesterol muscle statin |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.118.011662 |
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